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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Exploring Dysregulated Signaling Pathways in Cancer

Author(s): Sabah Nisar , Sheema Hashem, Muzafar A. Macha , Santosh K. Yadav, Sankavi Muralitharan , Lubna Therachiyil, Geetanjali Sageena, Hamda Al-Naemi, Mohammad Haris and Ajaz A. Bhat*

Volume 26, Issue 4, 2020

Page: [429 - 445] Pages: 17

DOI: 10.2174/1381612826666200115095937

Price: $65

Abstract

Cancer cell biology takes advantage of identifying diverse cellular signaling pathways that are disrupted in cancer. Signaling pathways are an important means of communication from the exterior of cell to intracellular mediators, as well as intracellular interactions that govern diverse cellular processes. Oncogenic mutations or abnormal expression of signaling components disrupt the regulatory networks that govern cell function, thus enabling tumor cells to undergo dysregulated mitogenesis, to resist apoptosis, and to promote invasion to neighboring tissues. Unraveling of dysregulated signaling pathways may advance the understanding of tumor pathophysiology and lead to the improvement of targeted tumor therapy. In this review article, different signaling pathways and how their dysregulation contributes to the development of tumors have been discussed.

Keywords: Angiogenesis, apoptosis, cell invasion, cell proliferation, drug targets, metastasis, signaling pathways, tumor microenvironment.

« Previous Next »
[1]
Garraway LA, Lander ES. Lessons from the cancer genome. Cell 2013; 153(1): 17-37.
[http://dx.doi.org/10.1016/j.cell.2013.03.002] [PMID: 23540688]
[2]
Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic signaling pathways in the cancer genome atlas Cell 2018; 173(2): 321-337. e10.
[http://dx.doi.org/10.1016/j.cell.2018.03.035] [PMID: 29625050]
[3]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[4]
Egeblad M, Nakasone ES, Werb Z. Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 2010; 18(6): 884-901.
[http://dx.doi.org/10.1016/j.devcel.2010.05.012] [PMID: 20627072]
[5]
Quezada SA, Peggs KS, Simpson TR, Allison JP. Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol Rev 2011; 241(1): 104-18.
[http://dx.doi.org/10.1111/j.1600-065X.2011.01007.x] [PMID: 21488893]
[6]
Giancotti FG. Deregulation of cell signaling in cancer. FEBS Lett 2014; 588(16): 2558-70.
[http://dx.doi.org/10.1016/j.febslet.2014.02.005] [PMID: 24561200]
[7]
Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harb Perspect Med 2015; 5(4)a006098
[http://dx.doi.org/10.1101/cshperspect.a006098] [PMID: 25833940]
[8]
Martin GS. Cell signaling and cancer. Cancer Cell 2003; 4(3): 167-74.
[http://dx.doi.org/10.1016/S1535-6108(03)00216-2] [PMID: 14522250]
[9]
Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 2009; 9(7): 463-75.
[http://dx.doi.org/10.1038/nrc2656] [PMID: 19536107]
[10]
Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol 2018; 12(1): 3-20.
[http://dx.doi.org/10.1002/1878-0261.12155] [PMID: 29124875]
[11]
Alowaidi F, Hashimi SM, Alqurashi N, Wood SA, Wei MQ. Cripto-1 overexpression in U87 glioblastoma cells activates MAPK, focal adhesion and ErbB pathways. Oncol Lett 2019; 18(3): 3399-406.
[http://dx.doi.org/10.3892/ol.2019.10626] [PMID: 31452820 ]
[12]
Testa JR, Tsichlis PN. AKT signaling in normal and malignant cells. Oncogene 2005; 24(50): 7391-3.
[http://dx.doi.org/10.1038/sj.onc.1209100] [PMID: 16288285]
[13]
Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 2001; 15(11): 1406-18.
[http://dx.doi.org/10.1101/gad.889901] [PMID: 11390360]
[14]
Chen H-T, Liu H, Mao M-J, et al. Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy. Mol Cancer 2019; 18(1): 101-.
[http://dx.doi.org/10.1186/s12943-019-1030-2] [PMID: 31126310]
[15]
Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res 2002; 90(12): 1243-50.
[http://dx.doi.org/10.1161/01.RES.0000022200.71892.9F] [PMID: 12089061]
[16]
Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol 2018; 15(5): 273-91.
[http://dx.doi.org/10.1038/nrclinonc.2018.28] [PMID: 29508857]
[17]
Owonikoko TK, Khuri FR. Targeting the PI3K/AKT/mTOR pathway: biomarkers of success and tribulation. American Society of Clinical Oncology educational book. Am Soc Clin Oncol 2013
[http://dx.doi.org/10.1200/EdBook_AM.2013.33. e395]
[18]
Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004; 304(5670): 554.
[http://dx.doi.org/10.1126/science.1096502] [PMID: 15016963]
[19]
Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502(7471): 333-9.
[http://dx.doi.org/10.1038/nature12634] [PMID: 24132290]
[20]
Vasko V, Saji M, Hardy E, et al. Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer. J Med Genet 2004; 41(3): 161-70.
[http://dx.doi.org/10.1136/jmg.2003.015339] [PMID: 14985374]
[21]
Ringel MD, Hayre N, Saito J, et al. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res 2001; 61(16): 6105-11.
[PMID: 11507060]
[22]
Miyakawa M, Tsushima T, Murakami H, Wakai K, Isozaki O, Takano K. Increased expression of phosphorylated p70S6 kinase and Akt in papillary thyroid cancer tissues. Endocr J 2003; 50(1): 77-83.
[http://dx.doi.org/10.1507/endocrj.50.77] [PMID: 12733712]
[23]
Blackhall FH, Pintilie M, Michael M, et al. Expression and prognostic significance of kit, protein kinase B, and mitogen-activated protein kinase in patients with small cell lung cancer. Clin Cancer Res 2003; 9(6): 2241-7.
[PMID: 12796392]
[24]
Balsara B, Pei J, Mitsuuchi Y, et al. Testa JRFrequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions. Carcinogenesis 2004; 25(11): 2053-9.
[http://dx.doi.org/10.1093/carcin/bgh226] [PMID: 15240509]
[25]
Lee SH, Kim HS, Park WS, et al. Non-small cell lung cancers frequently express phosphorylated Akt; an immunohistochemical study. APMIS 2002; 110(7-8): 587-92.
[http://dx.doi.org/10.1034/j.1600-0463.2002.11007811.x] [PMID: 12390418]
[26]
Tsao AS, McDonnell T, Lam S, et al. Increased Phospho-AKT (Ser<sup>473</sup>) expression in bronchial dysplasia. Cancer Epidemiology Biomarkers & amp;amp. Prevention 2003; 12: 660.
[PMID: 12869408]
[27]
Mukohara T1, Kudoh S, Matsuura K, et al.. Activated Akt Expression has Significant Correlation with EGFR and TGF-α Expressions in Stage I NSCLC. Anticancer Res 2004; 24: 11-8.
[28]
Stål O, Pérez-Tenorio G, Akerberg L, et al. Akt kinases in breast cancer and the results of adjuvant therapy. Breast Cancer Res 2003; 5(2): R37-44.
[http://dx.doi.org/10.1186/bcr569] [PMID: 12631397]
[29]
Pérez-Tenorio G, Stål O. Southeast sweden breast cancer G. activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 2002; 86(4): 540-5.
[http://dx.doi.org/10.1038/sj.bjc.6600126] [PMID: 11870534]
[30]
Shi W, Zhang X, Pintilie M, et al. Dysregulated PTEN-PKB and negative receptor status in human breast cancer. Int J Cancer 2003; 104(2): 195-203.
[http://dx.doi.org/10.1002/ijc.10909] [PMID: 12569575]
[31]
Sun M, Wang G, Paciga JE, et al. AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. Am J Pathol 2001; 159(2): 431-7.
[http://dx.doi.org/10.1016/S0002-9440(10)61714-2] [PMID: 11485901]
[32]
Nam SY, Lee HS, Jung G-A, et al. Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis. APMIS 2003; 111(12): 1105-13.
[http://dx.doi.org/10.1111/j.1600-0463.2003.apm1111205.x] [PMID: 14678019]
[33]
Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ. Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br J Cancer 2003; 89(11): 2110-5.
[http://dx.doi.org/10.1038/sj.bjc.6601396] [PMID: 14647146]
[34]
Semba S, Moriya T, Kimura W, Yamakawa M. Phosphorylated Akt/PKB controls cell growth and apoptosis in intraductal papillary-mucinous tumor and invasive ductal adenocarcinoma of the pancreas. Pancreas 2003; 26(3): 250-7.
[http://dx.doi.org/10.1097/00006676-200304000-00008] [PMID: 12657951]
[35]
Altomare DA, Wang HQ, Skele KL, et al. AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 2004; 23(34): 5853-7.
[http://dx.doi.org/10.1038/sj.onc.1207721] [PMID: 15208673]
[36]
Malik SN, Brattain M, Ghosh PM, et al. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clin Cancer Res 2002; 8(4): 1168-71.
[PMID: 11948129]
[37]
Horiguchi A, Oya M, Uchida A, Marumo K, Murai M. Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma. J Urol 2003; 169(2): 710-3.
[http://dx.doi.org/10.1016/S0022-5347(05)63998-5] [PMID: 12544348]
[38]
Terakawa N, Kanamori Y, Yoshida S. Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocr Relat Cancer 2003; 10(2): 203-8.
[http://dx.doi.org/10.1677/erc.0.0100203] [PMID: 12790783]
[39]
Chakravarti A, Zhai G, Suzuki Y, et al. The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. J Clin Oncol 2004; 22(10): 1926-33.
[http://dx.doi.org/10.1200/JCO.2004.07.193] [PMID: 15143086]
[40]
Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene 2005; 24(50): 7455-64.
[http://dx.doi.org/10.1038/sj.onc.1209085] [PMID: 16288292]
[41]
Qiang Yuan Z, Sun MI. Feldman R, Wang G, et al. Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer. Oncogene 19: 2324-30.
[42]
Altomare DA, Tanno S, De Rienzo A, et al. Frequent activation of AKT2 kinase in human pancreatic carcinomas. J Cell Biochem 2002; 87: 470-6.
[43]
Nakatani K, Thompson DA, Barthel A, et al. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J Biol Chem 1999; 274(31): 21528-32.
[http://dx.doi.org/10.1074/jbc.274.31.21528] [PMID: 10419456]
[44]
Carpten JD, Faber AL, Horn C, et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 2007; 448(7152): 439-44.
[http://dx.doi.org/10.1038/nature05933] [PMID: 17611497]
[45]
Staal SP. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci USA 1987; 84(14): 5034-7.
[http://dx.doi.org/10.1073/pnas.84.14.5034] [PMID: 3037531]
[46]
Shayesteh L, Lu Y, Kuo W-L, et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 1999; 21(1): 99-102.
[http://dx.doi.org/10.1038/5042] [PMID: 9916799]
[47]
Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2(7): 489-501.
[http://dx.doi.org/10.1038/nrc839] [PMID: 12094235]
[48]
Stefanetti RJ, Voisin S, Russell A, Lamon S. Recent advances in understanding the role of FOXO3. F1000 Res 2018; 7: F1000.
[49]
Moreira BP, Oliveira PF, Alves MG. Molecular mechanisms controlled by mTOR in male reproductive system. Int J Mol Sci 2019; 20(7): 1633.
[http://dx.doi.org/10.3390/ijms20071633] [PMID: 30986927]
[50]
Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 2014; 13(2): 140-56.
[http://dx.doi.org/10.1038/nrd4204] [PMID: 24481312]
[51]
Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012; 13(5): 283-96.
[http://dx.doi.org/10.1038/nrm3330] [PMID: 22473468]
[52]
Grumolato L, Aaronson SA. Aberrant signaling pathways in cancer. Holland Frei Cancer Med 2017.
[53]
Rapa I, Saggiorato E, Giachino D, et al. Mammalian target of rapamycin pathway activation is associated to RET mutation status in medullary thyroid carcinoma. J Clin Endocrinol Metab 2011; 96(7): 2146-53.
[http://dx.doi.org/10.1210/jc.2010-2655] [PMID: 21543427]
[54]
Miao H, Wei B-R, Peehl DM, et al. Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat Cell Biol 2001; 3(5): 527-30.
[http://dx.doi.org/10.1038/35074604] [PMID: 11331884]
[55]
McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007; 1773(8): 1263-84.
[http://dx.doi.org/10.1016/j.bbamcr.2006.10.001] [PMID: 17126425]
[56]
Fernández-Medarde A, Santos E. Ras in cancer and developmental diseases. Genes Cancer 2011; 2(3): 344-58.
[http://dx.doi.org/10.1177/1947601911411084] [PMID: 21779504]
[57]
Arrington AK, Heinrich EL, Lee W, et al. Prognostic and predictive roles of KRAS mutation in colorectal cancer. Int J Mol Sci 2012; 13(10): 12153-68.
[http://dx.doi.org/10.3390/ijms131012153] [PMID: 23202889]
[58]
Thumar J, Shahbazian D, Aziz SA, Jilaveanu LB, Kluger HM. MEK targeting in N-RAS mutated metastatic melanoma. Mol Cancer 2014; 13: 45-5.
[http://dx.doi.org/10.1186/1476-4598-13-45] [PMID: 24588908]
[59]
Muñoz-Couselo E, Adelantado EZ, Ortiz C, García JS, Perez-Garcia J. NRAS-mutant melanoma: current challenges and future prospect. OncoTargets Ther 2017; 10: 3941-7.
[http://dx.doi.org/10.2147/OTT.S117121] [PMID: 28860801]
[60]
Grünewald I, Vollbrecht C, Meinrath J, et al. Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity. Oncotarget 2015; 6(20): 18224-37.
[http://dx.doi.org/10.18632/oncotarget.4015] [PMID: 26053092]
[61]
Yoo J, Robinson RA. ras gene mutations in salivary gland tumors. Arch Pathol Lab Med 2000; 124(6): 836-9.
[PMID: 10835516]
[62]
Maurer G, Tarkowski B, Baccarini M. Raf kinases in cancer-roles and therapeutic opportunities. Oncogene 2011; 30(32): 3477-88.
[http://dx.doi.org/10.1038/onc.2011.160] [PMID: 21577205]
[63]
Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417(6892): 949-54.
[http://dx.doi.org/10.1038/nature00766] [PMID: 12068308]
[64]
Namba H, Nakashima M, Hayashi T, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab 2003; 88(9): 4393-7.
[http://dx.doi.org/10.1210/jc.2003-030305] [PMID: 12970315]
[65]
Jones JC, Renfro LA, Al-Shamsi HO, et al. Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer. J Clin Oncol 2017; 35(23): 2624-30.
[http://dx.doi.org/10.1200/JCO.2016.71.4394] [PMID: 28486044]
[66]
Cardarella S, Ogino A, Nishino M, et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clinical cancer research. Official J American Assoc Cancer Res 2013; 19: 4532-40.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0657]
[67]
Poulikakos PI, Rosen N. Mutant BRAF melanomas-dependence and resistance. Cancer Cell 2011; 19(1): 11-5.
[http://dx.doi.org/10.1016/j.ccr.2011.01.008] [PMID: 21251612]
[68]
Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 2007; 28(7): 742-62.
[http://dx.doi.org/10.1210/er.2007-0007] [PMID: 17940185]
[69]
Garnett MJ, Rana S, Paterson H, Barford D, Marais R. Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol Cell 2005; 20(6): 963-9.
[http://dx.doi.org/10.1016/j.molcel.2005.10.022] [PMID: 16364920]
[70]
Santarpia L, El-Naggar AK, Cote GJ, Myers JN, Sherman SI. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab 2008; 93(1): 278-84.
[http://dx.doi.org/10.1210/jc.2007-1076] [PMID: 17989125]
[71]
Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer 2009; 16(1): 17-44.
[http://dx.doi.org/10.1677/ERC-08-0154] [PMID: 18987168]
[72]
Beeram M, Patnaik A, Rowinsky EK. Raf: a strategic target for therapeutic development against cancer. J Clin Oncol 2005; 23(27): 6771-90.
[http://dx.doi.org/10.1200/JCO.2005.08.036] [PMID: 16170185]
[73]
Santarpia L, Lippman SM, El-Naggar AK. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16(1): 103-19.
[http://dx.doi.org/10.1517/14728222.2011.645805] [PMID: 22239440]
[74]
Fortini ME. Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 2009; 16(5): 633-47.
[http://dx.doi.org/10.1016/j.devcel.2009.03.010] [PMID: 19460341]
[75]
Tien A-C, Rajan A, Bellen HJ. A Notch updated. J Cell Biol 2009; 184(5): 621-9.
[http://dx.doi.org/10.1083/jcb.200811141] [PMID: 19255248]
[76]
Guo H, Lu Y, Wang J, et al. Targeting the notch signaling pathway in cancer therapeutics. Thorac Cancer 2014; 5(6): 473-86.
[http://dx.doi.org/10.1111/1759-7714.12143] [PMID: 26767041]
[77]
Leong KG, Niessen K, Kulic I, et al. Jagged1-mediated notch activation induces epithelial-to-mesenchymal transition through slug-induced repression of E-cadherin. J Exp Med 2007; 204(12): 2935-48.
[http://dx.doi.org/10.1084/jem.20071082] [PMID: 17984306]
[78]
Sethi S, Macoska J, Chen W, Sarkar FH. Molecular signature of epithelial-mesenchymal transition (EMT) in human prostate cancer bone metastasis. Am J Transl Res 2010; 3(1): 90-9.
[PMID: 21139809]
[79]
Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S. Intracellular cleavage of notch leads to a heterodimeric receptor on the plasma membrane. Cell 1997; 90(2): 281-91.
[http://dx.doi.org/10.1016/S0092-8674(00)80336-0] [PMID: 9244302]
[80]
Logeat F, Bessia C, Brou C, et al. The notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci USA 1998; 95(14): 8108-12.
[http://dx.doi.org/10.1073/pnas.95.14.8108] [PMID: 9653148]
[81]
Brou C, Logeat F, Gupta N, et al. A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 2000; 5(2): 207-16.
[http://dx.doi.org/10.1016/S1097-2765(00)80417-7] [PMID: 10882063]
[82]
De Strooper B, Annaert W, Cupers P, et al. A presenilin-1-dependent γ-secretase-like protease mediates release of notch intracellular domain. Nature 1999; 398(6727): 518-22.
[http://dx.doi.org/10.1038/19083] [PMID: 10206645]
[83]
Mumm JS, Schroeter EH, Saxena MT, et al. A ligand-induced extracellular cleavage regulates γ-secretase-like proteolytic activation of Notch1. Mol Cell 2000; 5(2): 197-206.
[http://dx.doi.org/10.1016/S1097-2765(00)80416-5] [PMID: 10882062]
[84]
Thompson BJ, Buonamici S, Sulis ML, et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med 2007; 204(8): 1825-35.
[http://dx.doi.org/10.1084/jem.20070872] [PMID: 17646408]
[85]
Bolós V, Mira E, Martínez-Poveda B, et al. Notch activation stimulates migration of breast cancer cells and promotes tumor growth. Breast Cancer Res 2013; 15(4): R54-4.
[http://dx.doi.org/10.1186/bcr3447] [PMID: 23826634]
[86]
Farnie G, Clarke RB. Mammary stem cells and breast cancer-role of notch signalling. Stem Cell Rev 2007; 3(2): 169-75.
[http://dx.doi.org/10.1007/s12015-007-0023-5] [PMID: 17873349]
[87]
Speiser JJ, Erşahin Ç, Osipo C. Chapter eleven - the functional role of notch signaling in triple-negative breast cancer. Vitam Horm 2013; 93: 277-306.
[88]
Stylianou S, Clarke RB, Brennan K. Aberrant activation of notch signaling in human breast cancer. Cancer Res 2006; 66(3): 1517-25.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3054] [PMID: 16452208]
[89]
Gallahan D, Kozak C, Callahan R. A new common integration region (int-3) for mouse mammary tumor virus on mouse chromosome 17. J Virol 1987; 61(1): 218-20.
[PMID: 3023699]
[90]
Pece S, Serresi M, Santolini E, et al. Loss of negative regulation by numb over notch is relevant to human breast carcinogenesis. J Cell Biol 2004; 167(2): 215-21.
[http://dx.doi.org/10.1083/jcb.200406140] [PMID: 15492044]
[91]
Weng AP, Millholland JM, Yashiro-Ohtani Y, et al. c-Myc is an important direct target of notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006; 20(15): 2096-109.
[http://dx.doi.org/10.1101/gad.1450406] [PMID: 16847353]
[92]
Beverly LJ, Felsher DW, Capobianco AJ. Suppression of p53 by notch in lymphomagenesis: implications for initiation and regression. Cancer Res 2005; 65(16): 7159-68.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1664] [PMID: 16103066]
[93]
Efstratiadis A, Szabolcs M, Klinakis A. Notch, Myc and breast cancer. Cell Cycle 2007; 6(4): 418-29.
[http://dx.doi.org/10.4161/cc.6.4.3838] [PMID: 17329972]
[94]
Phillips TM, Kim K, Vlashi E, McBride WH, Pajonk F. Effects of recombinant erythropoietin on breast cancer-initiating cells. Neoplasia 2007; 9(12): 1122-9.
[http://dx.doi.org/10.1593/neo.07694] [PMID: 18084619]
[95]
Wang Z, Zhang Y, Li Y, Banerjee S, Liao J, Sarkar FH. Down-regulation of notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther 2006; 5(3): 483-93.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0299] [PMID: 16546962]
[96]
Yabuuchi S, Pai SG, Campbell NR, et al. Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer. Cancer Lett 2013; 335(1): 41-51.
[http://dx.doi.org/10.1016/j.canlet.2013.01.054] [PMID: 23402814]
[97]
Hassan KA, Wang L, Korkaya H, et al. Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma. Clinical cancer research. Official J Am Assoc Cancer Res 2013; 19: 1972-80.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0370]
[98]
Razumilava N, Gores GJ. Notch-driven carcinogenesis: the merging of hepatocellular cancer and cholangiocarcinoma into a common molecular liver cancer subtype. J Hepatol 2013; 58(6): 1244-5.
[http://dx.doi.org/10.1016/j.jhep.2013.01.017] [PMID: 23352938]
[99]
Balint K, Xiao M, Pinnix CC, et al. Activation of notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. J Clin Invest 2005; 115(11): 3166-76.
[http://dx.doi.org/10.1172/JCI25001] [PMID: 16239965]
[100]
Liu Z-J, Xiao M, Balint K, et al. Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res 2006; 66(8): 4182-90.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3589] [PMID: 16618740]
[101]
Thomas SJ, Snowden JA, Zeidler MP, Danson SJ. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br J Cancer 2015; 113(3): 365-71.
[http://dx.doi.org/10.1038/bjc.2015.233] [PMID: 26151455]
[102]
Luo N, Balko JM. Role of JAK-STAT Pathway in Cancer Signaling InPredictive Biomarkers in Oncology. Springer Cham 2019; pp. 311-9.
[http://dx.doi.org/10.1007/978-3-319-95228-4_26]
[103]
Groner B, von Manstein V. Jak Stat signaling and cancer: opportunities, benefits and side effects of targeted inhibition. Mol Cell Endocrinol 2017; 451: 1-14.
[http://dx.doi.org/10.1016/j.mce.2017.05.033] [PMID: 28576744]
[104]
Verhoeven Y, Tilborghs S, Jacobs J, et al. The potential and controversy of targeting STAT family members in cancer Semin Cancer Biol 2019; pii: S1044-579X(19)30051-3 In Press
[http://dx.doi.org/10.1016/j.semcancer.2019.10.002] [PMID: 31605750]
[105]
Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009; 9(11): 798-809.
[http://dx.doi.org/10.1038/nrc2734] [PMID: 19851315]
[106]
Shahmarvand N, Nagy A, Shahryari J, Ohgami RS. Mutations in the signal transducer and activator of transcription family of genes in cancer. Cancer Sci 2018; 109(4): 926-33.
[http://dx.doi.org/10.1111/cas.13525] [PMID: 29417693]
[107]
Hsiao JR, Jin YT, Tsai ST, Shiau AL, Wu CL, Su WC. Constitutive activation of STAT3 and STAT5 is present in the majority of nasopharyngeal carcinoma and correlates with better prognosis. Br J Cancer 2003; 89(2): 344-9.
[http://dx.doi.org/10.1038/sj.bjc.6601003] [PMID: 12865928]
[108]
Nevalainen MT, Xie J, Torhorst J, et al. Signal transducer and activator of transcription-5 activation and breast cancer prognosis. J Clin Oncol 2004; 22(11): 2053-60.
[http://dx.doi.org/10.1200/JCO.2004.11.046] [PMID: 15169792]
[109]
Balko JM, Schwarz LJ, Luo N, et al. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2- specific dependence. Science translational medicine 2016; 8: 334. ra53-3.
[110]
Zimmers TA, Fishel ML, Bonetto A. STAT3 in the systemic inflammation of cancer cachexia. Semin Cell Dev Biol 2016; 54: 28-41.
[http://dx.doi.org/10.1016/j.semcdb.2016.02.009] [PMID: 26860754]
[111]
Taipale J, Beachy PA. The hedgehog and Wnt signalling pathways in cancer. Nature 2001; 411(6835): 349-54.
[http://dx.doi.org/10.1038/35077219] [PMID: 11357142]
[112]
Murone M, Rosenthal A, de Sauvage FJ. Hedgehog signal transduction: from flies to vertebrates. Exp Cell Res 1999; 253(1): 25-33.
[http://dx.doi.org/10.1006/excr.1999.4676] [PMID: 10579908]
[113]
Rubin LL, de Sauvage FJ. Targeting the hedgehog pathway in cancer. Nat Rev Drug Discov 2006; 5(12): 1026-33.
[http://dx.doi.org/10.1038/nrd2086] [PMID: 17139287]
[114]
Reifenberger J, Wolter M, Knobbe CB, et al. Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. Br J Dermatol 2005; 152(1): 43-51.
[http://dx.doi.org/10.1111/j.1365-2133.2005.06353.x] [PMID: 15656799]
[115]
Johnson RL, Rothman AL, Xie J, et al. Human homolog of a candidate gene for the basal cell nevus syndrome. Science 1996; 272(5268): 1668-71.
[http://dx.doi.org/10.1126/science.272.5268.1668] [PMID: 8658145]
[116]
Vorechovský I, Undén AB, Sandstedt B, Toftgård R, Ståhle-Bäckdahl M. Trichoepitheliomas contain somatic mutations in the overexpressed PTCH gene: support for a gatekeeper mechanism in skin tumorigenesis. Cancer Res 1997; 57(21): 4677-81.
[PMID: 9354420]
[117]
McGarvey TW, Maruta Y, Tomaszewski JE, Linnenbach AJ, Malkowicz SB. PTCH gene mutations in invasive transitional cell carcinoma of the bladder. Oncogene 1998; 17(9): 1167-72.
[http://dx.doi.org/10.1038/sj.onc.1202045] [PMID: 9764827]
[118]
Maesawa C, Tamura G, Iwaya T, et al. Mutations in the human homologue of the drosophila patched gene in esophageal squamous cell carcinoma. Genes Chromosomes Cancer 1998; 21(3): 276-9.
[http://dx.doi.org/10.1002/(SICI)1098-2264(199803)21:3<276:AID-GCC15>3.0.CO;2-N] [PMID: 9523206]
[119]
Almazán-Moga A, Zarzosa P, Molist C, et al. Ligand-dependent hedgehog pathway activation in rhabdomyosarcoma: the oncogenic role of the ligands. Br J Cancer 2017; 117(9): 1314-25.
[http://dx.doi.org/10.1038/bjc.2017.305] [PMID: 28881358]
[120]
Smyth I, Narang MA, Evans T, et al. Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol Genet 1999; 8(2): 291-7.
[http://dx.doi.org/10.1093/hmg/8.2.291] [PMID: 9931336]
[121]
Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003; 425(6960): 846-51.
[http://dx.doi.org/10.1038/nature01972] [PMID: 14520411]
[122]
Gulino A, Ferretti E, De Smaele E. Hedgehog signalling in colon cancer and stem cells. EMBO Mol Med 2009; 1(6-7): 300-2.
[http://dx.doi.org/10.1002/emmm.200900042] [PMID: 20049733]
[123]
Szkandera J, Kiesslich T, Haybaeck J, Gerger A, Pichler M. Hedgehog signaling pathway in ovarian cancer. Int J Mol Sci 2013; 14(1): 1179-96.
[http://dx.doi.org/10.3390/ijms14011179] [PMID: 23303278]
[124]
Kubo M, Nakamura M, Tasaki A, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 2004; 64(17): 6071-4.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0416] [PMID: 15342389]
[125]
Sheng T, Li C, Zhang X, et al. Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer 2004; 3: 29.
[http://dx.doi.org/10.1186/1476-4598-3-29] [PMID: 15482598]
[126]
Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003; 422(6929): 313-7.
[http://dx.doi.org/10.1038/nature01493] [PMID: 12629553]
[127]
O’Reilly KE, de Miera EV, Segura MF, et al. Hedgehog pathway blockade inhibits melanoma cell growth in vitro and in vivo. Pharmaceuticals (Basel) 2013; 6(11): 1429-50.
[http://dx.doi.org/10.3390/ph6111429] [PMID: 24287465]
[128]
Becher OJ, Hambardzumyan D, Fomchenko EI, et al. Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas. Cancer Res 2008; 68(7): 2241-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6350] [PMID: 18381430]
[129]
Monzo M, Moreno I, Artells R, et al. Sonic hedgehog mRNA expression by real-time quantitative PCR in normal and tumor tissues from colorectal cancer patients. Cancer Lett 2006; 233(1): 117-23.
[http://dx.doi.org/10.1016/j.canlet.2005.03.001] [PMID: 16473672]
[130]
Douard R, Moutereau S, Pernet P, et al. Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer. Surgery 2006; 139(5): 665-70.
[http://dx.doi.org/10.1016/j.surg.2005.10.012] [PMID: 16701100]
[131]
van den Brink GR, Bleuming SA, Hardwick JCH, et al. Indian hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat Genet 2004; 36(3): 277-82.
[http://dx.doi.org/10.1038/ng1304] [PMID: 14770182]
[132]
Akiyoshi T, Nakamura M, Koga K, et al. Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation. Gut 2006; 55(7): 991-9.
[http://dx.doi.org/10.1136/gut.2005.080333] [PMID: 16299030]
[133]
Fan L, Pepicelli CV, Dibble CC, et al. Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology 2004; 145(8): 3961-70.
[http://dx.doi.org/10.1210/en.2004-0079] [PMID: 15132968]
[134]
Theunissen J-W, de Sauvage FJ. Paracrine Hedgehog signaling in cancer. Cancer Res 2009; 69(15): 6007-10.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-0756] [PMID: 19638582]
[135]
Skoda AM, Simovic D, Karin V, Kardum V, Vranic S, Serman L. The role of the hedgehog signaling pathway in cancer: A comprehensive review. Bosn J Basic Med Sci 2018; 18(1): 8-20.
[http://dx.doi.org/10.17305/bjbms.2018.2756] [PMID: 29274272]
[136]
Lai S-L, Chien AJ, Moon RT. Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis. Cell Res 2009; 19(5): 532-45.
[http://dx.doi.org/10.1038/cr.2009.41] [PMID: 19365405]
[137]
Yamamoto S, Nishimura O, Misaki K, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell 2008; 15(1): 23-36.
[http://dx.doi.org/10.1016/j.devcel.2008.05.007] [PMID: 18606138]
[138]
van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development 2009; 136(19): 3205-14.
[http://dx.doi.org/10.1242/dev.033910] [PMID: 19736321]
[139]
Duchartre Y, Kim Y-M, Kahn M. The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol 2016; 99: 141-9.
[http://dx.doi.org/10.1016/j.critrevonc.2015.12.005] [PMID: 26775730]
[140]
Katoh M. Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. Int J Oncol 2003; 22(1): 209-12.
[http://dx.doi.org/10.3892/ijo.22.1.209] [PMID: 12469206]
[141]
You L, He B, Xu Z, et al. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene 2004; 23(36): 6170-4.
[http://dx.doi.org/10.1038/sj.onc.1207844] [PMID: 15208662]
[142]
Katoh M, Kirikoshi H, Terasaki H, Shiokawa K. WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT- β-catenin-TCF signaling pathway. Biochem Biophys Res Commun 2001; 289(5): 1093-8.
[http://dx.doi.org/10.1006/bbrc.2001.6076] [PMID: 11741304]
[143]
Verras M, Brown J, Li X, Nusse R, Sun Z. Wnt3a growth factor induces androgen receptor-mediated transcription and enhances cell growth in human prostate cancer cells. Cancer Res 2004; 64(24): 8860-6.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2370] [PMID: 15604245]
[144]
Flanagan D, Barker NS, Di Costanzo N, et al. Frizzled-7 is required for Wnt Signaling in gastric tumors with and without apc mutations. Cancer Res 2019; 79.
[145]
Terasaki H, Saitoh T, Shiokawa K, Katoh M. Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - β-catenin - TCF signaling pathway. Int J Mol Med 2002; 9(2): 107-12.
[http://dx.doi.org/10.3892/ijmm.9.2.107] [PMID: 11786918]
[146]
Okino K, Nagai H, Hatta M, et al. Up-regulation and overproduction of DVL-1, the human counterpart of the drosophila dishevelled gene, in cervical squamous cell carcinoma. Oncol Rep 2003; 10(5): 1219-23.
[http://dx.doi.org/10.3892/or.10.5.1219] [PMID: 12883684]
[147]
Uematsu K, Kanazawa S, You L, et al. Wnt pathway activation in mesothelioma: evidence of dishevelled overexpression and transcriptional activity of beta-catenin. Cancer Res 2003; 63(15): 4547-51.
[PMID: 12907630]
[148]
Suzuki H, Watkins DN, Jair K-W, et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet 2004; 36(4): 417-22.
[http://dx.doi.org/10.1038/ng1330] [PMID: 15034581]
[149]
Baylin SB, Ohm JE. Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 2006; 6(2): 107-16.
[http://dx.doi.org/10.1038/nrc1799] [PMID: 16491070]
[150]
Ying Y, Tao Q. Epigenetic disruption of the WNT/beta-catenin signaling pathway in human cancers 2009; 4(5): 307-12.
[151]
Saitoh T, Mine T, Katoh M. Frequent up-regulation of WNT5A mRNA in primary gastric cancer. Int J Mol Med 2002; 9(5): 515-9.
[http://dx.doi.org/10.3892/ijmm.9.5.515] [PMID: 11956659]
[152]
Vider BZ, Zimber A, Chastre E, et al. Evidence for the involvement of the Wnt 2 gene in human colorectal cancer. Oncogene 1996; 12(1): 153-8.
[PMID: 8552386]
[153]
Huang CL, Liu D, Nakano J, et al. Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor-an expression in non-small-cell lung cancer. J Clin Oncol 2005; 23(34): 8765-73.
[http://dx.doi.org/10.1200/JCO.2005.02.2871] [PMID: 16314637]
[154]
Ying J, Li H, Chen Y-W, Srivastava G, Gao Z, Tao Q. WNT5A is epigenetically silenced in hematologic malignancies and inhibits leukemia cell growth as a tumor suppressor. Blood 2007; 110(12): 4130-2.
[http://dx.doi.org/10.1182/blood-2007-06-094870] [PMID: 18024799]
[155]
Liang H, Chen Q, Coles AH, et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell 2003; 4(5): 349-60.
[http://dx.doi.org/10.1016/S1535-6108(03)00268-X] [PMID: 14667502]
[156]
Sato N, Fukushima N, Maitra A, et al. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res 2003; 63(13): 3735-42.
[PMID: 12839967]
[157]
Shu J, Jelinek J, Chang H, et al. Silencing of bidirectional promoters by DNA methylation in tumorigenesis. Cancer Res 2006; 66(10): 5077-84.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2629] [PMID: 16707430]
[158]
Chan SL, Cui Y, van Hasselt A, et al. The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. Lab Invest 2007; 87(7): 644-50.
[http://dx.doi.org/10.1038/labinvest.3700547] [PMID: 17384664]
[159]
Taniguchi H, Yamamoto H, Hirata T, et al. Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. Oncogene 2005; 24(53): 7946-52.
[http://dx.doi.org/10.1038/sj.onc.1208910] [PMID: 16007117]
[160]
Mazieres J, He B, You L, et al. Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res 2004; 64(14): 4717-20.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1389] [PMID: 15256437]
[161]
Román-Gómez J, Cordeu L, Agirre X, et al. Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia. Blood 2007; 109(8): 3462-9.
[http://dx.doi.org/10.1182/blood-2006-09-047043] [PMID: 17148581]
[162]
Sato H, Suzuki H, Toyota M, et al. Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors. Carcinogenesis 2007; 28(12): 2459-66.
[http://dx.doi.org/10.1093/carcin/bgm178] [PMID: 17675336]
[163]
Urakami S, Shiina H, Enokida H, et al. 770: Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder carcinogenesis through aberrant Wnt signaling activation. J Urol 2005; 173: 209.
[http://dx.doi.org/10.1016/S0022-5347(18)34939-5]
[164]
Zhang W, Glöckner SC, Guo M, et al. Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer. Cancer Res 2008; 68(8): 2764-72.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6349] [PMID: 18413743]
[165]
Fu D-Y, Wang Z-M. Li-Chen , et al Sox17, the canonical Wnt antagonist, is epigenetically inactivated by promoter methylation in human breast cancer. Breast Cancer Res Treat 2010; 119(3): 601-12.
[http://dx.doi.org/10.1007/s10549-009-0339-8] [PMID: 19301122]
[166]
Prasad CP, Mirza S, Sharma G, et al. Epigenetic alterations of CDH1 and APC genes: relationship with activation of Wnt/β-catenin pathway in invasive ductal carcinoma of breast. Life Sci 2008; 83(9-10): 318-25.
[http://dx.doi.org/10.1016/j.lfs.2008.06.019] [PMID: 18662704]
[167]
Wheeler JM, Kim HC, Efstathiou JA, Ilyas M, Mortensen NJ, Bodmer WF. Hypermethylation of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer. Gut 2001; 48(3): 367-71.
[http://dx.doi.org/10.1136/gut.48.3.367] [PMID: 11171827]
[168]
Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis. Exp Toxicol Pathol 2001; 53(4): 237-46.
[http://dx.doi.org/10.1078/0940-2993-00190] [PMID: 11665847]
[169]
Karin M, Cao Y, Greten FR, Li Z-W. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002; 2(4): 301-10.
[http://dx.doi.org/10.1038/nrc780] [PMID: 12001991]
[170]
Nakajima S, Kitamura M. Bidirectional regulation of NF-κB by reactive oxygen species: a role of unfolded protein response. Free Radic Biol Med 2013; 65: 162-74.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.06.020] [PMID: 23792277]
[171]
Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest 2001; 107(1): 7-11.
[http://dx.doi.org/10.1172/JCI11830] [PMID: 11134171]
[172]
Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 1994; 12: 141-79.
[http://dx.doi.org/10.1146/annurev.iy.12.040194.001041] [PMID: 8011280]
[173]
Park MH, Hong JT. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells 2016; 5(2): 15.
[http://dx.doi.org/10.3390/cells5020015] [PMID: 27043634]
[174]
Nelson DE, Ihekwaba AEC, Elliott M, et al. Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science 2004; 306(5696): 704-8.
[http://dx.doi.org/10.1126/science.1099962] [PMID: 15499023]
[175]
Gupta SC, Kim JH, Prasad S, Aggarwal BB. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev 2010; 29(3): 405-34.
[http://dx.doi.org/10.1007/s10555-010-9235-2] [PMID: 20737283]
[176]
Prasad S, Ravindran J, Aggarwal BB. NF-kappaB and cancer: how intimate is this relationship. Mol Cell Biochem 2010; 336(1-2): 25-37.
[http://dx.doi.org/10.1007/s11010-009-0267-2] [PMID: 19823771]
[177]
Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[κ]B activity. Annu Rev Immunol 2000; 18: 621-63.
[http://dx.doi.org/10.1146/annurev.immunol.18.1.621] [PMID: 10837071]
[178]
Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD. NF-κB in aging and disease. Aging Dis 2011; 2(6): 449-65.
[PMID: 22396894]
[179]
Sovak MA, Bellas RE, Kim DW, et al. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest 1997; 100(12): 2952-60.
[http://dx.doi.org/10.1172/JCI119848] [PMID: 9399940]
[180]
Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ Jr, Sledge GW Jr. Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 1997; 17(7): 3629-39.
[http://dx.doi.org/10.1128/MCB.17.7.3629] [PMID: 9199297]
[181]
Lind DS, Hochwald SN, Malaty J, et al. Nuclear factor-κ B is upregulated in colorectal cancer. Surgery 2001; 130(2): 363-9.
[http://dx.doi.org/10.1067/msy.2001.116672] [PMID: 11490372]
[182]
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140(6): 883-99.
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[183]
Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-α-induced cell death. Science 1996; 274(5288): 782-4.
[http://dx.doi.org/10.1126/science.274.5288.782] [PMID: 8864118]
[184]
Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-α-induced apoptosis by NF-kappaB. Science 1996; 274(5288): 787-9.
[http://dx.doi.org/10.1126/science.274.5288.787] [PMID: 8864120]
[185]
Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat Immunol 2002; 3(3): 221-7.
[http://dx.doi.org/10.1038/ni0302-221] [PMID: 11875461]
[186]
Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev 2010; 233(1): 233-55.
[http://dx.doi.org/10.1111/j.0105-2896.2009.00859.x] [PMID: 20193003]
[187]
Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 2014; 15(12): 1243-53.
[http://dx.doi.org/10.15252/embr.201439246] [PMID: 25381661]
[188]
Lane BR, Liu J, Bock PJ, et al. Interleukin-8 and growth-regulated oncogene alpha mediate angiogenesis in Kaposi’s sarcoma. J Virol 2002; 76(22): 11570-83.
[http://dx.doi.org/10.1128/JVI.76.22.11570-11583.2002] [PMID: 12388718]
[189]
Escárcega RO, Fuentes-Alexandro S, García-Carrasco M, Gatica A, Zamora A. The transcription factor nuclear factor-kappa B and cancer. Clin Oncol (R Coll Radiol) 2007; 19(2): 154-61.
[http://dx.doi.org/10.1016/j.clon.2006.11.013] [PMID: 17355113]
[190]
Yu S, Sun L, Jiao Y, Lee LTO. The role of G protein-coupled receptor kinases in cancer. Int J Biol Sci 2018; 14(2): 189-203.
[http://dx.doi.org/10.7150/ijbs.22896] [PMID: 29483837]
[191]
Katritch V, Cherezov V, Stevens RC. Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 2013; 53: 531-56.
[http://dx.doi.org/10.1146/annurev-pharmtox-032112-135923] [PMID: 23140243]
[192]
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM. Molecular signatures of G-protein-coupled receptors. Nature 2013; 494(7436): 185-94.
[http://dx.doi.org/10.1038/nature11896] [PMID: 23407534]
[193]
Hurowitz EH, Melnyk JM, Chen Y-J, Kouros-Mehr H, Simon MI, Shizuya H. Genomic characterization of the human heterotrimeric G protein α, β, and γ subunit genes. DNA Res 2000; 7(2): 111-20.
[http://dx.doi.org/10.1093/dnares/7.2.111] [PMID: 10819326]
[194]
Wang D. The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity. Immunopharmacol Immunotoxicol 2018; 40(3): 187-92.
[http://dx.doi.org/10.1080/08923973.2018.1434792] [PMID: 29433403]
[195]
Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002; 3(9): 639-50.
[http://dx.doi.org/10.1038/nrm908] [PMID: 12209124]
[196]
Neves SR, Ram PT, Iyengar R. G protein pathways. Science 2002; 296(5573): 1636-9.
[http://dx.doi.org/10.1126/science.1071550] [PMID: 12040175]
[197]
Wiley SZ, Sriram K, Salmerón C, Insel PA. GPR68: an emerging drug target in cancer. Int J Mol Sci 2019; 20(3): 559.
[http://dx.doi.org/10.3390/ijms20030559] [PMID: 30696114]
[198]
Wiley SZ, Sriram K, Liang W, et al. GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells. FASEB J 2018; 32(3): 1170-83.
[http://dx.doi.org/10.1096/fj.201700834R] [PMID: 29092903]
[199]
Horman SR, To J, Lamb J, et al. Functional profiling of microtumors to identify cancer associated fibroblast-derived drug targets. Oncotarget 2017; 8(59): 99913-30.
[http://dx.doi.org/10.18632/oncotarget.21915] [PMID: 29245949]
[200]
Wei W-C, Huang W-C, Lin Y-P, et al. Functional expression of calcium-permeable canonical transient receptor potential 4-containing channels promotes migration of medulloblastoma cells. J Physiol 2017; 595(16): 5525-44.
[http://dx.doi.org/10.1113/JP274659] [PMID: 28627017]
[201]
LaTulippe E, Satagopan J, Smith A, et al. Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res 2002; 62(15): 4499-506.
[PMID: 12154061]
[202]
Singh LS, Berk M, Oates R, et al. Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer. J Natl Cancer Inst 2007; 99(17): 1313-27.
[http://dx.doi.org/10.1093/jnci/djm107] [PMID: 17728215]
[203]
Ren J, Zhang L. Effects of ovarian cancer G protein coupled receptor 1 on the proliferation, migration, and adhesion of human ovarian cancer cells. Chin Med J (Engl) 2011; 124(9): 1327-32.
[PMID: 21740742]
[204]
Yan L, Singh LS, Zhang L, Xu Y. Role of OGR1 in myeloid-derived cells in prostate cancer. Oncogene 2014; 33(2): 157-64.
[http://dx.doi.org/10.1038/onc.2012.566] [PMID: 23222714]
[205]
Miller E, Yang J, DeRan M, et al. Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem Biol 2012; 19(8): 955-62.
[http://dx.doi.org/10.1016/j.chembiol.2012.07.005] [PMID: 22884261]
[206]
Mo J-S, Yu F-X, Gong R, Brown JH, Guan K-L. Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev 2012; 26(19): 2138-43.
[http://dx.doi.org/10.1101/gad.197582.112] [PMID: 22972936]
[207]
Moya IM, Halder G. Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol 2019; 20(4): 211-26.
[http://dx.doi.org/10.1038/s41580-018-0086-y] [PMID: 30546055]
[208]
Boopathy GTK, Hong W. Role of hippo pathway-YAP/TAZ signaling in angiogenesis. Front Cell Dev Biol 2019; 7: 49.
[http://dx.doi.org/10.3389/fcell.2019.00049] [PMID: 31024911]
[209]
Bar-Shavit R, Maoz M, Kancharla A, et al. G protein-coupled receptors in cancer. Int J Mol Sci 2016; 17(8): 1320.
[http://dx.doi.org/10.3390/ijms17081320] [PMID: 27529230]
[210]
Han Y. Analysis of the role of the hippo pathway in cancer. J Transl Med 2019; 17(1): 116-6.
[http://dx.doi.org/10.1186/s12967-019-1869-4] [PMID: 30961610]
[211]
Zanconato F, Cordenonsi M, Piccolo S. YAP/TAZ at the roots of cancer. Cancer Cell 2016; 29(6): 783-803.
[http://dx.doi.org/10.1016/j.ccell.2016.05.005] [PMID: 27300434]
[212]
Zhao B, Ye X, Yu J, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 2008; 22(14): 1962-71.
[http://dx.doi.org/10.1101/gad.1664408] [PMID: 18579750]
[213]
Holden JK, Cunningham CN. Targeting the hippo pathway and cancer through the TEAD family of transcription factors. Cancers (Basel) 2018; 10(3): 81.
[http://dx.doi.org/10.3390/cancers10030081] [PMID: 29558384]
[214]
Yu F-X, Zhao B, Panupinthu N, et al. Regulation of the hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 2012; 150(4): 780-91.
[http://dx.doi.org/10.1016/j.cell.2012.06.037] [PMID: 22863277]
[215]
Yu F-X, Luo J, Mo J-S, et al. Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 2014; 25(6): 822-30.
[http://dx.doi.org/10.1016/j.ccr.2014.04.017] [PMID: 24882516]
[216]
Pan D. The hippo signaling pathway in development and cancer. Dev Cell 2010; 19(4): 491-505.
[http://dx.doi.org/10.1016/j.devcel.2010.09.011] [PMID: 20951342]
[217]
Yu F-X, Zhang Y, Park HW, et al. Protein kinase a activates the hippo pathway to modulate cell proliferation and differentiation. Genes Dev 2013; 27(11): 1223-32.
[http://dx.doi.org/10.1101/gad.219402.113] [PMID: 23752589]
[218]
Ramos A, Camargo FD. The hippo signaling pathway and stem cell biology. Trends Cell Biol 2012; 22(7): 339-46.
[http://dx.doi.org/10.1016/j.tcb.2012.04.006] [PMID: 22658639]
[219]
Zhao B, Li L, Lei Q, Guan K-L. The hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev 2010; 24(9): 862-74.
[http://dx.doi.org/10.1101/gad.1909210] [PMID: 20439427]
[220]
Sudol M, Bork P, Einbond A, et al. Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. J Biol Chem 1995; 270(24): 14733-41.
[http://dx.doi.org/10.1074/jbc.270.24.14733] [PMID: 7782338]
[221]
Feng X, Degese MS, Iglesias-Bartolome R, et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 2014; 25(6): 831-45.
[http://dx.doi.org/10.1016/j.ccr.2014.04.016] [PMID: 24882515 ]
[222]
Park HW, Kim YC, Yu B, et al. Alternative Wnt signaling activates YAP/TAZ. Cell 2015; 162(4): 780-94.
[http://dx.doi.org/10.1016/j.cell.2015.07.013] [PMID: 26276632]
[223]
Fuchs SY, Adler V, Pincus MR, Ronai Z. MEKK1/JNK signaling stabilizes and activates p53. Proc Natl Acad Sci USA 1998; 95(18): 10541-6.
[http://dx.doi.org/10.1073/pnas.95.18.10541] [PMID: 9724739]
[224]
Fuchs SY, Dolan L, Davis RJ, Ronai Z. Phosphorylation-dependent targeting of c-Jun ubiquitination by Jun N-kinase. Oncogene 1996; 13(7): 1531-5.
[PMID: 8875991]
[225]
Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z. c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors. J Biol Chem 1997; 272(51): 32163-8.
[http://dx.doi.org/10.1074/jbc.272.51.32163] [PMID: 9405416]
[226]
Musti AM, Treier M, Bohmann D. Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases. Science 1997; 275(5298): 400-2.
[http://dx.doi.org/10.1126/science.275.5298.400] [PMID: 8994040]
[227]
Liu K-Q, Liu Z-P, Hao J-K, Chen L, Zhao X-M. Identifying dysregulated pathways in cancers from pathway interaction networks. BMC Bioinformatics 2012; 13: 126-6.
[http://dx.doi.org/10.1186/1471-2105-13-126] [PMID: 22676414]
[228]
English JM, Cobb MH. Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci 2002; 23(1): 40-5.
[http://dx.doi.org/10.1016/S0165-6147(00)01865-4] [PMID: 11804650]
[229]
Park J-I, Lee M-G, Cho K, et al. Transforming growth factor-β1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways. Oncogene 2003; 22(28): 4314-32.
[http://dx.doi.org/10.1038/sj.onc.1206478] [PMID: 12853969]
[230]
Khandrika L, Lieberman R, Koul S, et al. Hypoxia-associated p38 mitogen-activated protein kinase-mediated androgen receptor activation and increased HIF-1α levels contribute to emergence of an aggressive phenotype in prostate cancer. Oncogene 2009; 28(9): 1248-60.
[http://dx.doi.org/10.1038/onc.2008.476] [PMID: 19151763]
[231]
Maroni PD, Koul S, Meacham RB, Koul HK. Mitogen activated protein kinase signal transduction pathways in the prostate. Cell Commun Signal 2004; 2(1): 5-5.
[http://dx.doi.org/10.1186/1478-811X-2-5] [PMID: 15219238]
[232]
Tsai P-W, Shiah S-G, Lin M-T, Wu C-W, Kuo M-L. Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-β 1. A critical role of p38/nuclear factor-κ B signaling pathway. J Biol Chem 2003; 278(8): 5750-9.
[http://dx.doi.org/10.1074/jbc.M204863200] [PMID: 12471041]
[233]
Suarez-Cuervo C, Merrell MA, Watson L, et al. Breast cancer cells with inhibition of p38α have decreased MMP-9 activity and exhibit decreased bone metastasis in mice. Clin Exp Metastasis 2004; 21(6): 525-33.
[http://dx.doi.org/10.1007/s10585-004-3503-x] [PMID: 15679050]
[234]
Kumar B, Koul S, Petersen J, et al. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Cancer Res 2010; 70(2): 832-41.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2918] [PMID: 20068172]
[235]
Iyoda K, Sasaki Y, Horimoto M, et al. Involvement of the p38 mitogen-activated protein kinase cascade in hepatocellular carcinoma. Cancer 2003; 97(12): 3017-26.
[http://dx.doi.org/10.1002/cncr.11425] [PMID: 12784337]
[236]
Greenberg AK, Basu S, Hu J, et al. Selective p38 activation in human non-small cell lung cancer. Am J Respir Cell Mol Biol 2002; 26(5): 558-64.
[http://dx.doi.org/10.1165/ajrcmb.26.5.4689] [PMID: 11970907]
[237]
Elenitoba-Johnson KSJ, Jenson SD, Abbott RT, et al. Involvement of multiple signaling pathways in follicular lymphoma transformation: p38-mitogen-activated protein kinase as a target for therapy. Proc Natl Acad Sci USA 2003; 100(12): 7259-64.
[http://dx.doi.org/10.1073/pnas.1137463100] [PMID: 12756297]
[238]
Lin Z, Crockett DK, Jenson SD, Lim MS, Elenitoba-Johnson KSJ. Quantitative proteomic and transcriptional analysis of the response to the p38 mitogen-activated protein kinase inhibitor SB203580 in transformed follicular lymphoma cells. Mol Cell Proteomics 2004; 3(8): 820-33.
[http://dx.doi.org/10.1074/mcp.M400008-MCP200] [PMID: 15169874]
[239]
Bhowmick NA, Ghiassi M, Bakin A, et al. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 2001; 12(1): 27-36.
[http://dx.doi.org/10.1091/mbc.12.1.27] [PMID: 11160820]
[240]
Bhowmick NA, Zent R, Ghiassi M, McDonnell M, Moses HL. Integrin β 1 signaling is necessary for transforming growth factor-β activation of p38MAPK and epithelial plasticity. J Biol Chem 2001; 276(50): 46707-13.
[http://dx.doi.org/10.1074/jbc.M106176200] [PMID: 11590169]
[241]
Sosa MS, Avivar-Valderas A, Bragado P, Wen H-C, Aguirre-Ghiso JA. ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin Cancer Research. Official J Am Assoc Cancer Research 2011; 17: 5850-7.
[242]
Cheng Y, Qiu F, Tashiro S, Onodera S, Ikejima T. ERK and JNK mediate TNFalpha-induced p53 activation in apoptotic and autophagic L929 cell death. Biochem Biophys Res Commun 2008; 376(3): 483-8.
[http://dx.doi.org/10.1016/j.bbrc.2008.09.018] [PMID: 18796294]
[243]
Cheng T-L, Symons M, Jou T-S. Regulation of anoikis by Cdc42 and Rac1. Exp Cell Res 2004; 295(2): 497-511.
[http://dx.doi.org/10.1016/j.yexcr.2004.02.002] [PMID: 15093747]
[244]
Ellinger-Ziegelbauer H, Kelly K, Siebenlist U. Cell cycle arrest and reversion of Ras-induced transformation by a conditionally activated form of mitogen-activated protein kinase kinase kinase 3. Mol Cell Biol 1999; 19(5): 3857-68.
[http://dx.doi.org/10.1128/MCB.19.5.3857] [PMID: 10207109]
[245]
Pruitt K, Pruitt WM, Bilter GK, Westwick JK, Der CJ. Raf-independent deregulation of p38 and JNK mitogen-activated protein kinases are critical for Ras transformation. J Biol Chem 2002; 277(35): 31808-17.
[http://dx.doi.org/10.1074/jbc.M203964200] [PMID: 12082106 ]
[246]
Bulavin DV, Fornace AJ. p38 MAP kinase's emerging role as a tumor suppressor. Adv Cancer Res. Academic Press 2004; (92): 95- 118.
[247]
Kummer JL, Rao PK, Heidenreich KA. Apoptosis induced by withdrawal of trophic factors is mediated by p38 mitogen-activated protein kinase. J Biol Chem 1997; 272(33): 20490-4.
[http://dx.doi.org/10.1074/jbc.272.33.20490] [PMID: 9252360]
[248]
She Q-B, Bode AM, Ma W-Y, Chen N-Y, Dong Z. Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res 2001; 61(4): 1604-10.
[PMID: 11245472]
[249]
Bradham C, McClay DR. p38 MAPK in development and cancer. Cell Cycle 2006; 5(8): 824-8.
[http://dx.doi.org/10.4161/cc.5.8.2685] [PMID: 16627995]
[250]
Bulavin DV, Demidov ON, Saito S, et al. Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet 2002; 31(2): 210-5.
[http://dx.doi.org/10.1038/ng894] [PMID: 12021785]
[251]
Brancho D, Tanaka N, Jaeschke A, et al. Mechanism of p38 MAP kinase activation in vivo. Genes Dev 2003; 17(16): 1969-78.
[http://dx.doi.org/10.1101/gad.1107303] [PMID: 12893778]
[252]
Timofeev O, Lee TY, Bulavin DV. A subtle change in p38 MAPK activity is sufficient to suppress in vivo tumorigenesis. Cell Cycle 2005; 4(1): 118-20.
[http://dx.doi.org/10.4161/cc.4.1.1342] [PMID: 15611662]
[253]
Koul HK, Pal M, Koul S. Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer 2013; 4(9-10): 342-59.
[http://dx.doi.org/10.1177/1947601913507951] [PMID: 24349632]
[254]
Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer 2009; 9(10): 749-58.
[http://dx.doi.org/10.1038/nrc2723] [PMID: 19776744]
[255]
Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992; 69(7): 1237-45.
[http://dx.doi.org/10.1016/0092-8674(92)90644-R] [PMID: 1535557]
[256]
Barak Y, Juven T, Haffner R, Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J 1993; 12(2): 461-8.
[http://dx.doi.org/10.1002/j.1460-2075.1993.tb05678.x] [PMID: 8440237]
[257]
Manfredi JJ. The Mdm2-p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor. Genes Dev 2010; 24(15): 1580-9.
[http://dx.doi.org/10.1101/gad.1941710] [PMID: 20679392]
[258]
Wade M, Wang YV, Wahl GM. The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol 2010; 20(5): 299-309.
[http://dx.doi.org/10.1016/j.tcb.2010.01.009] [PMID: 20172729]
[259]
Mendoza M, Mandani G, Momand J. The MDM2 gene family. Biomol Concepts 2014; 5(1): 9-19.
[http://dx.doi.org/10.1515/bmc-2013-0027] [PMID: 25372739]
[260]
Mandinova A, Lee SW. The p53 pathway as a target in cancer therapeutics: obstacles and promise Science translational medicine 2011; 3: 64. rv1.
[http://dx.doi.org/10.1126/scitranslmed.3001366]
[261]
Laptenko O, Prives C. Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ 2006; 13(6): 951-61.
[http://dx.doi.org/10.1038/sj.cdd.4401916] [PMID: 16575405]
[262]
Kruse J-P, Gu W. Modes of p53 regulation. Cell 2009; 137(4): 609-22.
[http://dx.doi.org/10.1016/j.cell.2009.04.050] [PMID: 19450511]
[263]
Gasco M, Shami S, Crook T. The p53 pathway in breast cancer. Breast Cancer Res 2002; 4(2): 70-6.
[http://dx.doi.org/10.1186/bcr426] [PMID: 11879567]
[264]
Slattery ML, Mullany LE, Wolff RK, Sakoda LC, Samowitz WS, Herrick JS. The p53-signaling pathway and colorectal cancer: Interactions between downstream p53 target genes and miRNAs. Genomics 2019; 111(4): 762-71.
[http://dx.doi.org/10.1016/j.ygeno.2018.05.006] [PMID: 29860032]
[265]
Xiang J-F, Wang W-Q, Liu L, et al. Mutant p53 determines pancreatic cancer poor prognosis to pancreatectomy through upregulation of cavin-1 in patients with preoperative serum CA19-9≥1,000U/mL. Sci Rep 2016; 6: 19222.
[http://dx.doi.org/10.1038/srep19222] [PMID: 26753987]
[266]
Corney DC, Flesken-Nikitin A, Choi J, Nikitin AY. Role of p53 and Rb in ovarian cancer. Adv Exp Med Biol 2008; 622: 99-117.
[http://dx.doi.org/10.1007/978-0-387-68969-2_9] [PMID: 18546622]
[267]
Gibbons DL, Byers LA, Kurie JM. Smoking, p53 mutation, and lung cancer. Mol Cancer Res 2014; 12(1): 3-13.
[http://dx.doi.org/10.1158/1541-7786.MCR-13-0539] [PMID: 24442106]
[268]
Gasco M, Crook T. The p53 network in head and neck cancer. Oral Oncol 2003; 39(3): 222-31.
[http://dx.doi.org/10.1016/S1368-8375(02)00163-X] [PMID: 12618194]
[269]
Jiménez C, Portela RA, Mellado M, et al. Role of the PI3K regulatory subunit in the control of actin organization and cell migration. J Cell Biol 2000; 151(2): 249-62.
[http://dx.doi.org/10.1083/jcb.151.2.249] [PMID: 11038173]
[270]
Jin L, Zhou Y. Crucial role of the pentose phosphate pathway in malignant tumors. Oncol Lett 2019; 17(5): 4213-21.
[http://dx.doi.org/10.3892/ol.2019.10112] [PMID: 30944616]
[271]
Cho ES, Cha YH, Kim HS, Kim NH, Yook JI. The pentose phosphate pathway as a potential target for cancer therapy. Biomol Ther (Seoul) 2018; 26(1): 29-38.
[http://dx.doi.org/10.4062/biomolther.2017.179] [PMID: 29212304]
[272]
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324(5930): 1029-33.
[http://dx.doi.org/10.1126/science.1160809] [PMID: 19460998]
[273]
Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol 2017; 14(1): 11-31.
[http://dx.doi.org/10.1038/nrclinonc.2016.60] [PMID: 27141887]
[274]
Lu M, Lu L, Dong Q, et al. Elevated G6PD expression contributes to migration and invasion of hepatocellular carcinoma cells by inducing epithelial-mesenchymal transition. Acta Biochim Biophys Sin (Shanghai) 2018; 50(4): 370-80.
[http://dx.doi.org/10.1093/abbs/gmy009] [PMID: 29471502]
[275]
DeWaal D, Nogueira V, Terry AR, et al. Hexokinase-2 depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin. Nat Commun 2018; 9(1): 446-6.
[http://dx.doi.org/10.1038/s41467-017-02733-4] [PMID: 29386513]
[276]
Dong T, Kang X, Liu Z, et al. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer. Tumour Biol 2016; 37(6): 8159-68.
[http://dx.doi.org/10.1007/s13277-015-4729-8] [PMID: 26715276]
[277]
Pu H, Zhang Q, Zhao C, et al. Overexpression of G6PD is associated with high risks of recurrent metastasis and poor progression-free survival in primary breast carcinoma. World J Surg Oncol 2015; 13: 323-.
[http://dx.doi.org/10.1186/s12957-015-0733-0] [PMID: 26607846]
[278]
Benito A, Polat IH, Noé V, Ciudad CJ, Marin S, Cascante M. Glucose-6-phosphate dehydrogenase and transketolase modulate breast cancer cell metabolic reprogramming and correlate with poor patient outcome. Oncotarget 2017; 8(63): 106693-706.
[http://dx.doi.org/10.18632/oncotarget.21601] [PMID: 29290982]
[279]
Yang X, Peng X, Huang J. Inhibiting 6-phosphogluconate dehydrogenase selectively targets breast cancer through AMPK activation. Clin Transl Oncol 2018; 20(9): 1145-52.
[http://dx.doi.org/10.1007/s12094-018-1833-4] [PMID: 29340974]
[280]
Giatromanolaki A, Sivridis E, Arelaki S, Koukourakis MI. Expression of enzymes related to glucose metabolism in non-small cell lung cancer and prognosis. Exp Lung Res 2017; 43(4-5): 167-74.
[http://dx.doi.org/10.1080/01902148.2017.1328714] [PMID: 28644754]
[281]
Hong W, Cai P, Xu C, et al. Inhibition of glucose-6-phosphate dehydrogenase reverses cisplatin resistance in lung cancer cells via the redox system. Front Pharmacol 2018; 9: 43-3.
[http://dx.doi.org/10.3389/fphar.2018.00043] [PMID: 29445340]
[282]
Zheng W, Feng Q, Liu J, et al. Inhibition of 6-phosphogluconate dehydrogenase reverses cisplatin resistance in ovarian and lung cancer. Front Pharmacol 2017; 8: 421-1.
[http://dx.doi.org/10.3389/fphar.2017.00421] [PMID: 28713273]
[283]
Chan B, VanderLaan PA, Sukhatme VP. 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met. Biochem Biophys Res Commun 2013; 439(2): 247-51.
[http://dx.doi.org/10.1016/j.bbrc.2013.08.048] [PMID: 23973484]
[284]
Marbaniang C, Kma L. Dysregulation of glucose metabolism by oncogenes and tumor suppressors in cancer cells. Asian Pac J Cancer Prev 2018; 19(9): 2377-90.
[PMID: 30255690]
[285]
Miller DM, Thomas SD, Islam A, Muench D, Sedoris K. c-Myc and cancer metabolism. Clin Cancer Res 2012; 18(20): 5546-53.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0977] [PMID: 23071356]
[286]
Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 2009; 15(21): 6479-83.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0889] [PMID: 19861459]
[287]
Nagao A, Kobayashi M, Koyasu S, Chow CCT, Harada H. HIF-1-dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance. Int J Mol Sci 2019; 20(2): 238.
[http://dx.doi.org/10.3390/ijms20020238] [PMID: 30634433]
[288]
Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006; 3(3): 177-85.
[http://dx.doi.org/10.1016/j.cmet.2006.02.002] [PMID: 16517405]
[289]
Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006; 3(3): 187-97.
[http://dx.doi.org/10.1016/j.cmet.2006.01.012] [PMID: 16517406]
[290]
Furuta E, Pai SK, Zhan R, et al. Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 2008; 68(4): 1003-11.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2489] [PMID: 18281474]
[291]
Stine ZE, Walton ZE, Altman BJ, Hsieh AL, Dang CV. MYC, metabolism, and cancer. Cancer Discov 2015; 5(10): 1024-39.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0507] [PMID: 26382145]
[292]
Prendergast GC, Ziff EB. A new bind for Myc. Trends Genet 1992; 8(3): 91-6.
[http://dx.doi.org/10.1016/0168-9525(92)90196-B] [PMID: 1579994]
[293]
Choi Y-K, Park K-G. Targeting glutamine metabolism for cancer treatment. Biomol Ther (Seoul) 2018; 26(1): 19-28.
[http://dx.doi.org/10.4062/biomolther.2017.178] [PMID: 29212303]
[294]
Wang T, Liu H, Lian G, Zhang S-Y, Wang X, Jiang C. HIF1α-induced glycolysis metabolism is essential to the activation of inflammatory macrophages. Mediators Inflamm 2017; 2017: 9029327-7.
[http://dx.doi.org/10.1155/2017/9029327] [PMID: 29386753]
[295]
Zimna A, Kurpisz M. Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis: applications and therapies. BioMed Res Int 2015; 2015: 549412-2.
[http://dx.doi.org/10.1155/2015/549412] [PMID: 26146622]
[296]
Bensaad K, Favaro E, Lewis CA, et al. Fatty acid uptake and lipid storage induced by HIF-1α contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep 2014; 9(1): 349-65.
[http://dx.doi.org/10.1016/j.celrep.2014.08.056] [PMID: 25263561]
[297]
Dai M-S, Lu H. Crosstalk between c-Myc and ribosome in ribosomal biogenesis and cancer. J Cell Biochem 2008; 105(3): 670-7.
[http://dx.doi.org/10.1002/jcb.21895] [PMID: 18773413]
[298]
Schmidt EV. The role of c-myc in regulation of translation initiation. Oncogene 2004; 23(18): 3217-21.
[http://dx.doi.org/10.1038/sj.onc.1207548] [PMID: 15094771]
[299]
Carrella D, Manni I, Tumaini B, et al. Computational drugs repositioning identifies inhibitors of oncogenic PI3K/AKT/P70S6K-dependent pathways among FDA-approved compounds. Oncotarget 2016; 7(37): 58743-58.
[http://dx.doi.org/10.18632/oncotarget.11318] [PMID: 27542212]
[300]
Hiraki M, Hwang S-Y, Cao S, et al. Small-molecule reactivation of mutant p53 to wild-type-like p53 through the p53-Hsp40 regulatory axis. Chem Biol 2015; 22(9): 1206-16.
[http://dx.doi.org/10.1016/j.chembiol.2015.07.016] [PMID: 26320861]
[301]
Soragni A, Janzen DM, Johnson LM, et al. A designed inhibitor of p53 aggregation rescues p53 tumor suppression in ovarian carcinomas. Cancer Cell 2016; 29(1): 90-103.
[http://dx.doi.org/10.1016/j.ccell.2015.12.002] [PMID: 26748848]
[302]
Cicenas J, Zalyte E, Rimkus A, Dapkus D, Noreika R, Urbonavicius S. JNK, p38, ERK, and SGK1 inhibitors in cancer. Cancers (Basel) 2017; 10(1): 1.
[http://dx.doi.org/10.3390/cancers10010001] [PMID: 29267206]
[303]
Grassi ES, Vezzoli V, Negri I, et al. SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways. Oncotarget 2015; 6(34): 36383-99.
[http://dx.doi.org/10.18632/oncotarget.5799] [PMID: 26415230]
[304]
Kim J-H, Kim TH, Kang HS, Ro J, Kim HS, Yoon S. SP600125, an inhibitor of Jnk pathway, reduces viability of relatively resistant cancer cells to doxorubicin. Biochem Biophys Res Commun 2009; 387(3): 450-5.
[http://dx.doi.org/10.1016/j.bbrc.2009.07.036] [PMID: 19607816]
[305]
Kim J-H, Chae M, Choi A-R, Sik Kim H, Yoon S. SP600125 overcomes antimitotic drug-resistance in cancer cells by increasing apoptosis with independence of P-gp inhibition. Eur J Pharmacol 2014; 723: 141-7.
[http://dx.doi.org/10.1016/j.ejphar.2013.11.026] [PMID: 24333214]
[306]
Lu Y-Y, Chen T-S, Wang X-P, Qu J-L, Chen M. The JNK inhibitor SP600125 enhances dihydroartemisinin-induced apoptosis by accelerating Bax translocation into mitochondria in human lung adenocarcinoma cells. FEBS Lett 2010; 584(18): 4019-26.
[http://dx.doi.org/10.1016/j.febslet.2010.08.014] [PMID: 20709060]
[307]
Lin Y, Zhang B, Liang H, et al. JNK inhibitor SP600125 enhances TGF-β-induced apoptosis of RBE human cholangiocarcinoma cells in a Smad-dependent manner. Mol Med Rep 2013; 8(6): 1623-9.
[http://dx.doi.org/10.3892/mmr.2013.1711] [PMID: 24100678]
[308]
Jemaà M, Vitale I, Kepp O, et al. Selective killing of p53-deficient cancer cells by SP600125. EMBO Mol Med 2012; 4(6): 500-14.
[http://dx.doi.org/10.1002/emmm.201200228] [PMID: 22438244]
[309]
Konno T, Ninomiya T, Kohno T, Kikuchi S, Sawada N, Kojima T. c-Jun N-terminal kinase inhibitor SP600125 enhances barrier function and elongation of human pancreatic cancer cell line HPAC in a Ca-switch model. Histochem Cell Biol 2015; 143(5): 471-9.
[http://dx.doi.org/10.1007/s00418-014-1300-4] [PMID: 25511417]
[310]
Li JY, Huang JY, Xing B, et al. SP600125, a JNK inhibitor, suppresses growth of JNK-inactive glioblastoma cells through cell-cycle G2/M phase arrest. Pharmazie 2012; 67(11): 942-6.
[PMID: 23210245]
[311]
Yasui H, Hideshima T, Ikeda H, et al. BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth. Br J Haematol 2007; 136(3): 414-23.
[http://dx.doi.org/10.1111/j.1365-2141.2006.06443.x] [PMID: 17173546]
[312]
He D, Zhao XQ, Chen XG, et al. BIRB796, the inhibitor of p38 mitogen-activated protein kinase, enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cells. PLoS One 2013; 8(1): e54181-1.
[http://dx.doi.org/10.1371/journal.pone.0054181] [PMID: 23349819]
[313]
Porta C, Paglino C, Mosca A. targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 2014; 4: 64-4.
[http://dx.doi.org/10.3389/fonc.2014.00064] [PMID: 24782981]
[314]
Belyea B, Kephart JG, Blum J, Kirsch DG, Linardic CM. Embryonic signaling pathways and rhabdomyosarcoma: contributions to cancer development and opportunities for therapeutic targeting. Sarcoma 2012; 2012: 406239-9.
[http://dx.doi.org/10.1155/2012/406239] [PMID: 22619564]
[315]
Lee SM, Moon J, Redman BG, et al. Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933. Cancer 2015; 121(3): 432-40.
[http://dx.doi.org/10.1002/cncr.29055] [PMID: 25250858]
[316]
Zhang M, Mathews Griner LA, Ju W, et al. Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia. Proc Natl Acad Sci USA 2015; 112(40): 12480-5.
[http://dx.doi.org/10.1073/pnas.1516208112] [PMID: 26396258]
[317]
Zimmerli D, Cecconi V, Valenta T, et al. WNT ligands control initiation and progression of human papillomavirus-driven squamous cell carcinoma. Oncogene 2018; 37(27): 3753-62.
[http://dx.doi.org/10.1038/s41388-018-0244-x] [PMID: 29662191]
[318]
Zhong Z, Sepramaniam S, Chew XH, et al. PORCN inhibition synergizes with PI3K/mTOR inhibition in Wnt-addicted cancers. Oncogene 2019; 38(40): 6662-77.
[http://dx.doi.org/10.1038/s41388-019-0908-1] [PMID: 31391551]
[319]
Canesin G, Evans-Axelsson S, Hellsten R, et al. Treatment with the WNT5A-mimicking peptide foxy-5 effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model. PLoS One 2017; 12(9) e0184418
[http://dx.doi.org/10.1371/journal.pone.0184418] [PMID: 28886116]
[320]
Tornatore L, Sandomenico A, Raimondo D, et al. Cancer-selective targeting of the NF-κB survival pathway with GADD45β/MKK7 inhibitors. Cancer Cell 2014; 26(4): 495-508.
[http://dx.doi.org/10.1016/j.ccr.2014.07.027] [PMID: 25314077]
[321]
Yong H-Y, Koh M-S, Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin Investig Drugs 2009; 18(12): 1893-905.
[http://dx.doi.org/10.1517/13543780903321490] [PMID: 19852565]
[322]
Luistro L, He W, Smith M, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res 2009; 69(19): 7672-80.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-1843] [PMID: 19773430]
[323]
O’Shea JJ, Pesu M, Borie DC, Changelian PS. A new modality for immunosuppression: targeting the JAK/STAT pathway. Nat Rev Drug Discov 2004; 3(7): 555-64.
[http://dx.doi.org/10.1038/nrd1441] [PMID: 15232577]

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