Login Register Cart 0
Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Molecular Biomarkers for Lung Adenocarcinoma: A Short Review

Author(s): Srikumar Chakravarthi* and Barani Karikalan

Volume 17, Issue 2, 2021

Published on: 24 July, 2020

Page: [97 - 106] Pages: 10

DOI: 10.2174/1573394716666200724164654

Price: $65

Abstract

Lung cancer is a disease with higher death rates and is responsible for around 2 million deaths per year worldwide. Recently, several breakthroughs have been made in the field of lung cancer that has led to a revolution in the management of lung cancer patients. Identification of molecular markers and the implication of respective targeted therapies has been a great success in the treatment of lung adenocarcinoma patients. Despite the fact that targeted therapy of lung adenocarcinomas represents one of the significant milestones in the treatment of lung cancer that resulted in increased survival rates even in advanced stages, the mortality rates of lung cancer still remain to be significantly high. This warrants further research for gaining better insights into molecular alterations that can lead to newer innovations in targeted drug therapy towards lung adenocarcinoma. In this review, we briefly summarized the literature on molecular markers that are already in use. We also consolidated newer molecular markers that are under study with the potential for being targeted for therapies in future.

Keywords: Molecular markers, molecular/genetic alterations, genetic markers, target therapy, lung adenocarcinoma, nonsmall cell lung cancer.

« Previous Next »
Graphical Abstract

[1]
Oberndorfer F, Müllauer L. Molecular pathology of lung cancer: Current status and perspectives. Curr Opin Oncol 2018; 30(2): 69-76.
[http://dx.doi.org/10.1097/CCO.0000000000000429] [PMID: 29251665]
[2]
Domagala-Kulawik J. New frontiers for molecular pathology. Front Med (Lausanne) 2019; 6: 284.
[http://dx.doi.org/10.3389/fmed.2019.00284] [PMID: 31867335]
[3]
Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: Epidemiology, etiology, and prevention. Clin Chest Med 2011; 32(4): 605-44.
[http://dx.doi.org/10.1016/j.ccm.2011.09.001] [PMID: 22054876]
[4]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[5]
Reck M, Heigener DF, Mok T, Soria JC, Rabe KF. Management of non-small-cell lung cancer: Recent developments. Lancet 2013; 382(9893): 709-19.
[http://dx.doi.org/10.1016/S0140-6736(13)61502-0] [PMID: 23972814]
[6]
Reck M, Rabe KF. Advanced non-small-cell lung cancer. N Engl J Med 2017; 377(20): 1999.
[PMID: 29141160]
[7]
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361(10): 947-57.
[http://dx.doi.org/10.1056/NEJMoa0810699] [PMID: 19692680]
[8]
Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The eighth edition lung cancer stage classification Chest In: 2017; 151: pp. 193-203.
[9]
Matěj R, Rohan Z, Němejcová K, Dundr P. Molecular pathology of lung cancer in routine diagnostic practice: 2017 update. Cesk Patol 2017; 53(4): 159-66.
[PMID: 29227119]
[10]
Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl Lung Cancer Res 2015; 4(1): 36-54.
[PMID: 25806345]
[11]
Saito M, Shiraishi K, Kunitoh H, Takenoshita S, Yokota J, Kohno T. Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci 2016; 107(6): 713-20.
[http://dx.doi.org/10.1111/cas.12941] [PMID: 27027665]
[12]
Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448(7153): 561-6.
[http://dx.doi.org/10.1038/nature05945] [PMID: 17625570]
[13]
Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368(25): 2385-94.
[http://dx.doi.org/10.1056/NEJMoa1214886] [PMID: 23724913]
[14]
Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007; 131(6): 1190-203.
[http://dx.doi.org/10.1016/j.cell.2007.11.025] [PMID: 18083107]
[15]
Kohno T, Ichikawa H, Totoki Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med 2012; 18(3): 375-7.
[http://dx.doi.org/10.1038/nm.2644] [PMID: 22327624]
[16]
Uguen A, De Braekeleer M. ROS1 fusions in cancer: A review. Future Oncol 2016; 12(16): 1911-28.
[http://dx.doi.org/10.2217/fon-2016-0050] [PMID: 27256160]
[17]
Mulligan LM. RET revisited: Expanding the oncogenic portfolio. Nat Rev Cancer 2014; 14(3): 173-86.
[http://dx.doi.org/10.1038/nrc3680] [PMID: 24561444]
[18]
Birchmeier C, Sharma S, Wigler M. Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proc Natl Acad Sci USA 1987; 84(24): 9270-4.
[http://dx.doi.org/10.1073/pnas.84.24.9270] [PMID: 2827175]
[19]
Kohno T, Nakaoku T, Tsuta K, et al. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res 2015; 4(2): 156-64.
[PMID: 25870798]
[20]
Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009; 27(26): 4247-53.
[http://dx.doi.org/10.1200/JCO.2009.22.6993] [PMID: 19667264]
[21]
Hirsch FR, Suda K, Wiens J, Bunn PA Jr. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet 2016; 388(10048): 1012-24.
[http://dx.doi.org/10.1016/S0140-6736(16)31473-8] [PMID: 27598681]
[22]
Pendharkar D, Ausekar BV, Gupta S. Molecular biology of lung cancer-a review. Indian J Surg Oncol 2013; 4(2): 120-4.
[http://dx.doi.org/10.1007/s13193-013-0213-3] [PMID: 24426712]
[23]
Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 2006; 38(7): 787-93.
[http://dx.doi.org/10.1038/ng1834] [PMID: 16804544]
[24]
Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing M. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: A systematic review and meta-analysis. Medicine (Baltimore) 2012; 91(5): 274-86.
[http://dx.doi.org/10.1097/MD.0b013e31826a9c71] [PMID: 22932786]
[25]
Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: A meta-analysis. Br J Dermatol 2011; 164(4): 776-84.
[http://dx.doi.org/10.1111/j.1365-2133.2010.10185.x] [PMID: 21166657]
[26]
Nakayama N, Nakayama K, Yeasmin S, et al. KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer. Br J Cancer 2008; 99(12): 2020-8.
[http://dx.doi.org/10.1038/sj.bjc.6604783] [PMID: 19018267]
[27]
Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: A single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 2016; 17(5): 642-50.
[http://dx.doi.org/10.1016/S1470-2045(16)00077-2] [PMID: 27080216]
[28]
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]
[29]
Hirsch FR, Varella-Garcia M, Franklin WA, et al. Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas. Br J Cancer 2002; 86(9): 1449-56.
[http://dx.doi.org/10.1038/sj.bjc.6600286] [PMID: 11986780]
[30]
Pellegrini C, Falleni M, Marchetti A, et al. HER-2/Neu alterations in non-small cell lung cancer: A comprehensive evaluation by real time reverse transcription-PCR, fluorescence in situ hybridization, and immunohistochemistry. Clin Cancer Res 2003; 9(10 Pt 1): 3645-52.
[PMID: 14506153]
[31]
Heinmöller P, Gross C, Beyser K, et al. HER2 status in non-small cell lung cancer: Results from patient screening for enrollment to a phase II study of herceptin. Clin Cancer Res 2003; 9(14): 5238-43.
[PMID: 14614004]
[32]
Mar N, Vredenburgh JJ, Wasser JS. Targeting HER2 in the treatment of non-small cell lung cancer. Lung Cancer 2015; 87(3): 220-5.
[http://dx.doi.org/10.1016/j.lungcan.2014.12.018] [PMID: 25601485]
[33]
Yoshizawa A, Sumiyoshi S, Sonobe M, et al. HER2 status in lung adenocarcinoma: A comparison of immunohistochemistry, fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations. Lung Cancer 2014; 85(3): 373-8.
[http://dx.doi.org/10.1016/j.lungcan.2014.06.007] [PMID: 25047676]
[34]
Nakamura H, Kawasaki N, Taguchi M, Kabasawa K. Association of HER-2 overexpression with prognosis in nonsmall cell lung carcinoma: A metaanalysis. Cancer 2005; 103(9): 1865-73.
[http://dx.doi.org/10.1002/cncr.20957] [PMID: 15770690]
[35]
Mazières J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation: Epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013; 31(16): 1997-2003.
[http://dx.doi.org/10.1200/JCO.2012.45.6095] [PMID: 23610105]
[36]
Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 2012; 18(18): 4910-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0912] [PMID: 22761469]
[37]
Lara PN Jr, Laptalo L, Longmate J, et al. California Cancer Consortium. Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: A California Cancer Consortium screening and phase II trial. Clin Lung Cancer 2004; 5(4): 231-6.
[http://dx.doi.org/10.3816/CLC.2004.n.004] [PMID: 14967075]
[38]
Langer CJ, Stephenson P, Thor A, Vangel M, Johnson DH. Eastern Cooperative Oncology Group Study 2598. Trastuzumab in the treatment of advanced non-small-cell lung cancer: Is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J Clin Oncol 2004; 22(7): 1180-7.
[http://dx.doi.org/10.1200/JCO.2004.04.105] [PMID: 14981103]
[39]
Gatzemeier U, Groth G, Butts C, et al. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol 2004; 15(1): 19-27.
[http://dx.doi.org/10.1093/annonc/mdh031] [PMID: 14679114]
[40]
Clamon G, Herndon J, Kern J, et al. Cancer and Leukemia Group B. Lack of trastuzumab activity in nonsmall cell lung carcinoma with overexpression of erb-B2: 39810: A phase II trial of Cancer and Leukemia Group B. Cancer 2005; 103(8): 1670-5.
[http://dx.doi.org/10.1002/cncr.20950] [PMID: 15751020]
[41]
De Grève J, Teugels E, Geers C, et al. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer 2012; 76(1): 123-7.
[http://dx.doi.org/10.1016/j.lungcan.2012.01.008] [PMID: 22325357]
[42]
Trusolino L, Bertotti A, Comoglio PM. MET signalling: Principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 2010; 11(12): 834-48.
[http://dx.doi.org/10.1038/nrm3012] [PMID: 21102609]
[43]
Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: Rationale and progress. Nat Rev Cancer 2012; 12(2): 89-103.
[http://dx.doi.org/10.1038/nrc3205] [PMID: 22270953]
[44]
Eder JP, Vande Woude GF, Boerner SA, LoRusso PM. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin Cancer Res 2009; 15(7): 2207-14.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1306] [PMID: 19318488]
[45]
Cancer Genome Atlas Research N. Comprehensive molecular profiling of LAC. Nature 2014; 511: 543-50.
[46]
Denisenko TV, Budkevich IN, Zhivotovsky B. Cell death-based treatment of lung adenocarcinoma. Cell Death Dis 2018; 9(2): 117.
[http://dx.doi.org/10.1038/s41419-017-0063-y] [PMID: 29371589]
[47]
Paik PK, Drilon A, Fan PD, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discov 2015; 5(8): 842-9.
[http://dx.doi.org/10.1158/2159-8290.CD-14-1467] [PMID: 25971939]
[48]
Plenker D, Bertrand M, de Langen AJ, et al. Structural alterations of MET trigger response to MET kinase inhibition in lung adenocarcinoma patients. Clin Cancer Res 2018; 24(6): 1337-43.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3001] [PMID: 29284707]
[49]
Jahangiri A, Nguyen A, Chandra A, et al. Cross-activating c-Met/β1 integrin complex drives metastasis and invasive resistance in cancer. Proc Natl Acad Sci USA 2017; 114(41): E8685-94.
[http://dx.doi.org/10.1073/pnas.1701821114] [PMID: 28973887]
[50]
Acunzo M, Romano G, Palmieri D, et al. Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2. Proc Natl Acad Sci USA 2013; 110(21): 8573-8.
[http://dx.doi.org/10.1073/pnas.1302107110] [PMID: 23650389]
[51]
Garofalo M, Romano G, Di Leva G, et al. EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med 2011; 18(1): 74-82.
[http://dx.doi.org/10.1038/nm.2577] [PMID: 22157681]
[52]
Zhang P, Li S, Lv C, et al. BPI-9016M, a c-Met inhibitor, suppresses tumor cell growth, migration and invasion of lung adenocarcinoma via miR203-DKK1. Theranostics 2018; 8(21): 5890-902.
[http://dx.doi.org/10.7150/thno.27667] [PMID: 30613269]
[53]
Walter DM, Venancio OS, Buza EL, et al. Systematic in vivo inactivation of chromatin-regulating enzymes identifies Setd2 as a potent tumor suppressor in lung adenocarcinoma. Cancer Res 2017; 77(7): 1719-29.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2159] [PMID: 28202515]
[54]
Herpel E, Rieker RJ, Dienemann H, et al. SMARCA4 and SMARCA2 deficiency in non-small cell lung cancer: Immunohistochemical survey of 316 consecutive specimens. Ann Diagn Pathol 2017; 26: 47-51.
[http://dx.doi.org/10.1016/j.anndiagpath.2016.10.006] [PMID: 28038711]
[55]
Kadoch C, Hargreaves DC, Hodges C, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet 2013; 45(6): 592-601.
[http://dx.doi.org/10.1038/ng.2628] [PMID: 23644491]
[56]
Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011; 11(7): 481-92.
[http://dx.doi.org/10.1038/nrc3068] [PMID: 21654818]
[57]
Wilson BG, Wang X, Shen X, et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 2010; 18(4): 316-28.
[http://dx.doi.org/10.1016/j.ccr.2010.09.006] [PMID: 20951942]
[58]
Stanton BZ, Hodges C, Calarco JP, et al. Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin. Nat Genet 2016; 49(2): 282-8.
[PMID: 27941795]
[59]
Kadoch C, Williams R, Calarco JP, et al. Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat Genet 2017; 49(2): 213-22.
[PMID: 27941796]
[60]
Wang X, Lee RS, Alver BH, et al. SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation. Nat Genet 2017; 49(2): 289-95.
[PMID: 27941797]
[61]
Mathur R, Alver BH, Roman AKS, et al. ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice. Nat Genet 2017; 49(2): 296-302.
[PMID: 27941798]
[62]
Hoffman GR, Rahal R, Buxton F, et al. Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers. Proc Natl Acad Sci USA 2014; 111(8): 3128-33.
[http://dx.doi.org/10.1073/pnas.1316793111] [PMID: 24520176]
[63]
Helming KC, Wang X, Wilson BG, et al. ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat Med 2014; 20(3): 251-4.
[http://dx.doi.org/10.1038/nm.3480] [PMID: 24562383]
[64]
Nambirajan A, Singh V, Bhardwaj N, Mittal S, Kumar S, Jain D. SMARCA4/BRG1-deficient non-small cell lung carcinomas: A case series and review of the literature. Arch Pathol Lab Med 2020. [Epub ahead of print].
[http://dx.doi.org/10.5858/arpa.2019-0633-OA] [PMID: 32271611]
[65]
Johnson BE. Divide and conquer to treat lung cancer. N Engl J Med 2016; 375(19): 1892-3.
[http://dx.doi.org/10.1056/NEJMe1611003] [PMID: 27718875]
[66]
Wang L, Cui Y, Sheng J, et al. Epigenetic inactivation of HOXA11, a novel functional tumor suppressor for renal cell carcinoma, is associated with RCC TNM classification. Oncotarget 2017; 8(13): 21861-70.
[http://dx.doi.org/10.18632/oncotarget.15668] [PMID: 28423531]
[67]
Se YB, Kim SH, Kim JY, et al. Underexpression of HOXA11 is associated with treatment resistance and poor prognosis in glioblastoma. Cancer Res Treat 2017; 49(2): 387-98.
[http://dx.doi.org/10.4143/crt.2016.106] [PMID: 27456940]
[68]
Whitcomb BP, Mutch DG, Herzog TJ, Rader JS, Gibb RK, Goodfellow PJ. Frequent HOXA11 and THBS2 promoter methylation, and a methylator phenotype in endometrial adenocarcinoma. Clin Cancer Res 2003; 9(6): 2277-87.
[PMID: 12796396]
[69]
Speleman F, Cauwelier B, Dastugue N, et al. A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. Leukemia 2005; 19(3): 358-66.
[http://dx.doi.org/10.1038/sj.leu.2403657] [PMID: 15674412]
[70]
Tao MH, Freudenheim JL. DNA methylation in endometrial cancer. Epigenetics 2010; 5(6): 491-8.
[http://dx.doi.org/10.4161/epi.5.6.12431] [PMID: 20543579]
[71]
Xia B, Shan M, Wang J, et al. Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer. Oncotarget 2017; 8(6): 9794-805.
[http://dx.doi.org/10.18632/oncotarget.14216] [PMID: 28038461]
[72]
Hwang JA, Lee BB, Kim Y, et al. HOXA11 hypermethylation is associated with progression of non-small cell lung cancer. Oncotarget 2013; 4(12): 2317-25.
[http://dx.doi.org/10.18632/oncotarget.1464] [PMID: 24259349]
[73]
Li Q, Chen C, Ren X, Sun W. DNA methylation profiling identifies the HOXA11 gene as an early diagnostic and prognostic molecular marker in human lung adenocarcinoma. Oncotarget 2017; 8(20): 33100-9.
[http://dx.doi.org/10.18632/oncotarget.16528] [PMID: 28380439]
[74]
Yang X, Deng Y, He R-Q, et al. Upregulation of HOXA11 during the progression of lung adenocarcinoma detected via multiple approaches. Int J Mol Med 2018; 42(5): 2650-64.
[http://dx.doi.org/10.3892/ijmm.2018.3826] [PMID: 30106131]
[75]
Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407(6801): 258-64.
[http://dx.doi.org/10.1038/35025229] [PMID: 11001069]
[76]
Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64(6): 1057-68.
[http://dx.doi.org/10.1016/0092-8674(91)90261-V] [PMID: 1672265]
[77]
Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, Kuliopulos A. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 2005; 120(3): 303-13.
[http://dx.doi.org/10.1016/j.cell.2004.12.018] [PMID: 15707890]
[78]
Grisaru-Granovsky S, Salah Z, Maoz M, Pruss D, Beller U, Bar-Shavit R. Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples. Int J Cancer 2005; 113(3): 372-8.
[http://dx.doi.org/10.1002/ijc.20607] [PMID: 15455382]
[79]
Massi D, Naldini A, Ardinghi C, et al. Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma. Hum Pathol 2005; 36(6): 676-85.
[http://dx.doi.org/10.1016/j.humpath.2005.04.008] [PMID: 16021575]
[80]
Black PC, Mize GJ, Karlin P, et al. Overexpression of protease-activated receptors-1,-2, and-4 (PAR-1, -2, and -4) in prostate cancer. Prostate 2007; 67(7): 743-56.
[http://dx.doi.org/10.1002/pros.20503] [PMID: 17373694]
[81]
Cisowski J, O’Callaghan K, Kuliopulos A, et al. Targeting protease-activated receptor-1 with cell-penetrating pepducins in lung cancer. Am J Pathol 2011; 179(1): 513-23.
[http://dx.doi.org/10.1016/j.ajpath.2011.03.025] [PMID: 21703428]
[82]
Fujimoto D, Hirono Y, Goi T, Katayama K, Yamaguchi A. Prognostic value of protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1) in gastric cancer. Anticancer Res 2008; 28(2A): 847-54.
[PMID: 18507028]
[83]
Villares GJ, Zigler M, Wang H, et al. Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA. Cancer Res 2008; 68(21): 9078-86.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-2397] [PMID: 18974154]
[84]
Wu Z, Zeng Y, Zhong M, Wang B. Targeting A549 lung adenocarcinoma cell growth and invasion with protease-activated receptor-1 siRNA. Mol Med Rep 2014; 9(5): 1787-93.
[http://dx.doi.org/10.3892/mmr.2014.2023] [PMID: 24604247]
[85]
Ferrer I, Verdugo-Sivianes EM, Castilla MA, et al. Loss of the tumor suppressor spinophilin (PPP1R9B) increases the cancer stem cell population in breast tumors. Oncogene 2016; 35(21): 2777-88.
[http://dx.doi.org/10.1038/onc.2015.341] [PMID: 26387546]
[86]
Verdugo-Sivianes EM, Navas L, Molina-Pinelo S, et al. Coordinated downregulation of Spinophilin and the catalytic subunits of PP1, PPP1CA/B/C, contributes to a worse prognosis in lung cancer. Oncotarget 2017; 8(62): 105196-210.
[http://dx.doi.org/10.18632/oncotarget.22111] [PMID: 29285244]
[87]
Vuadens F, Rufer N, Kress A, Corthésy P, Schneider P, Tissot JD. Identification of swiprosin 1 in human lymphocytes. Proteomics 2004; 4(8): 2216-20.
[http://dx.doi.org/10.1002/pmic.200300779] [PMID: 15274114]
[88]
Vega IE. EFhd2, a protein linked to Alzheimer’s disease and other neurological disorders. Front Neurosci 2016; 10: 150.
[http://dx.doi.org/10.3389/fnins.2016.00150] [PMID: 27064956]
[89]
Kroczek C, Lang C, Brachs S, et al. Swiprosin-1/EFhd2 controls B cell receptor signaling through the assembly of the B cell receptor, Syk, and phospholipase C Gamma2 in membrane rafts. J Immunol 2010; 184(7): 3665-76.
[http://dx.doi.org/10.4049/jimmunol.0903642] [PMID: 20194721]
[90]
Huh YH, Oh S, Yeo YR, et al. Swiprosin-1 stimulates cancer invasion and metastasis by increasing the Rho family of GTPase signaling. Oncotarget 2015; 6(15): 13060-71.
[http://dx.doi.org/10.18632/oncotarget.3637] [PMID: 26079945]
[91]
Fan CC, Cheng WC, Huang YC, et al. EFHD2 promotes epithelial-to-mesenchymal transition and correlates with postsurgical recurrence of stage I lung adenocarcinoma. Sci Rep 2017; 7(1): 14617.
[http://dx.doi.org/10.1038/s41598-017-15186-y] [PMID: 29097801]
[92]
Montero JC, Rodríguez-Barrueco R, Ocaña A, Díaz-Rodríguez E, Esparís-Ogando A, Pandiella A. Neuregulins and cancer. Clin Cancer Res 2008; 14(11): 3237-41.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5133] [PMID: 18519747]
[93]
Wilson TR, Lee DY, Berry L, Shames DS, Settleman J. Neuregulin-1-mediated autocrine signaling underlies sensitivity to HER2 kinase inhibitors in a subset of human cancers. Cancer Cell 2011; 20(2): 158-72.
[http://dx.doi.org/10.1016/j.ccr.2011.07.011] [PMID: 21840482]
[94]
Matkar S, Sharma P, Gao S, et al. An epigenetic pathway regulates sensitivity of breast cancer cells to HER2 inhibition via FOXO/c-Myc axis. Cancer Cell 2015; 28(4): 472-85.
[http://dx.doi.org/10.1016/j.ccell.2015.09.005] [PMID: 26461093]
[95]
Gay ND, Wang Y, Beadling C, et al. Durable response to Afatinib in lung adenocarcinoma harboring NRG1 gene fusions. J Thorac Oncol 2017; 12(8): e107-10.
[http://dx.doi.org/10.1016/j.jtho.2017.04.025] [PMID: 28502724]
[96]
Jones MR, Lim H, Shen Y, et al. Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer. Ann Oncol 2017; 28(12): 3092-7.
[http://dx.doi.org/10.1093/annonc/mdx523] [PMID: 28950338]
[97]
Hidai C, Kawana M, Kitano H, Kokubun S. Discoidin domain of Del1 protein contributes to its deposition in the extracellular matrix. Cell Tissue Res 2007; 330(1): 83-95.
[http://dx.doi.org/10.1007/s00441-007-0456-9] [PMID: 17701220]
[98]
Ho HK, Jang JJ, Kaji S, et al. Developmental endothelial locus-1 (Del-1), a novel angiogenic protein: Its role in ischemia. Circulation 2004; 109(10): 1314-9.
[http://dx.doi.org/10.1161/01.CIR.0000118465.36018.2D] [PMID: 14981004]
[99]
Aoka Y, Johnson FL, Penta K, et al. The embryonic angiogenic factor Del1 accelerates tumor growth by enhancing vascular formation. Microvasc Res 2002; 64(1): 148-61.
[http://dx.doi.org/10.1006/mvre.2002.2414] [PMID: 12074641]
[100]
Xia H, Chen J, Shi M, et al. EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma. J Hepatol 2015; 63(4): 863-73.
[http://dx.doi.org/10.1016/j.jhep.2015.05.005] [PMID: 25980764]
[101]
Lee SH, Kim DY, Jing F, et al. Del-1 overexpression potentiates lung cancer cell proliferation and invasion. Biochem Biophys Res Commun 2015; 468(1-2): 92-8.
[http://dx.doi.org/10.1016/j.bbrc.2015.10.159] [PMID: 26545781]
[102]
Jeong D, Ban S, Oh S, Jin Lee S, Yong Park S, Koh YW. Prognostic significance of EDIL3 expression and correlation with mesenchymal phenotype and microvessel density in lung adenocarcinoma. Sci Rep 2017; 7(1): 8649.
[http://dx.doi.org/10.1038/s41598-017-08851-9] [PMID: 28819306]
[103]
Miller WE, Lefkowitz RJ. Expanding roles for β-arrestins as scaffolds and adapters in GPCR signaling and trafficking. Curr Opin Cell Biol 2001; 13(2): 139-45.
[http://dx.doi.org/10.1016/S0955-0674(00)00190-3] [PMID: 11248546]
[104]
DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK. Beta-arrestins and cell signaling. Annu Rev Physiol 2007; 69: 483-510.
[http://dx.doi.org/10.1146/annurev.physiol.69.022405.154749] [PMID: 17305471]
[105]
Li X, Che K, Wang L, et al. Subcellular localization of β-arrestin1 and its prognostic value in lung adenocarcinoma. Medicine (Baltimore) 2017; 96(45): e8450.
[http://dx.doi.org/10.1097/MD.0000000000008450] [PMID: 29137031]
[106]
El-Khoury V, Béland M, Schritz A, et al. Identification of beta-arrestin-1 as a diagnostic biomarker in lung cancer. Br J Cancer 2018; 119(5): 580-90.
[http://dx.doi.org/10.1038/s41416-018-0200-0] [PMID: 30078843]
[107]
Yuan W, Zhang X, Xu Y, Li S, Hu Y, Wu S. Role of HOXB7 in regulation of progression and metastasis of human lung adenocarcinoma. Mol Carcinog 2014; 53(1): 49-57.
[http://dx.doi.org/10.1002/mc.21947] [PMID: 22911672]
[108]
Zhuang L, Li WH, Li K, Mao Y, Gao CL. Zhang C1.Hoxb7 promotes growth and metastasis of lac cells through regulation of the Tgf-β/Smad3 signaling. J Biol Regul Homeost Agents 2015; 29(3): 601-8.
[PMID: 26403398]
[109]
Monterisi S, Lo Riso P, Russo K, et al. HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype. Oncogene 2018; 37(26): 3575-88.
[http://dx.doi.org/10.1038/s41388-018-0229-9] [PMID: 29576613]
[110]
Mollinedo F, Gajate C. Lipid rafts as major platforms for signaling regulation in cancer. Adv Biol Regul 2015; 57: 130-46.
[http://dx.doi.org/10.1016/j.jbior.2014.10.003] [PMID: 25465296]
[111]
Staubach S, Hanisch FG. Lipid rafts: Signaling and sorting platforms of cells and their roles in cancer. Expert Rev Proteomics 2011; 8(2): 263-77.
[http://dx.doi.org/10.1586/epr.11.2] [PMID: 21501018]
[112]
Kostadinova A, Topouzova-Hristova T, Momchilova A, Tzoneva R, Berger MR. Antitumor lipids: Structure, functions, and medical applications. Adv Protein Chem Struct Biol 2015; 101: 27-66.
[http://dx.doi.org/10.1016/bs.apcsb.2015.08.001] [PMID: 26572975]
[113]
Li H, Wang RM, Liu SG, et al. Abnormal expression of FLOT1 correlates with tumor progression and poor survival in patients with non-small cell lung cancer. Tumour Biol 2014; 35(4): 3311-5.
[http://dx.doi.org/10.1007/s13277-013-1434-3] [PMID: 24277378]
[114]
Li L, Luo J, Wang B, et al. Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer. Mol Cancer 2013; 12: 163.
[http://dx.doi.org/10.1186/1476-4598-12-163] [PMID: 24330780]
[115]
Li Z, Yang Y, Gao Y, et al. Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer. Am J Cancer Res 2015; 6(1): 38-50.
[PMID: 27073721]
[116]
Zhang SH, Wang CJ, Shi L, et al. High expression of FLOT1 is associated with progression and poor prognosis in hepatocellular carcinoma. PLoS One 2013; 8(6): e64709.
[http://dx.doi.org/10.1371/journal.pone.0064709] [PMID: 23840303]
[117]
Deng Y, Ge P, Tian T, et al. Prognostic value of flotillins (flotillin-1 and flotillin-2) in human cancers: A meta-analysis. Clin Chim Acta 2018; 481: 90-8.
[http://dx.doi.org/10.1016/j.cca.2018.02.036] [PMID: 29499201]
[118]
Ou YX, Liu FT, Chen FY, Zhu ZM. Prognostic value of Flotillin-1 expression in patients with solid tumors. Oncotarget 2017; 8(32): 52665-77.
[http://dx.doi.org/10.18632/oncotarget.17075] [PMID: 28881760]
[119]
Zhang L, Mao Y, Mao Q, et al. FLOT1 promotes tumor development, induces epithelial-mesenchymal transition, and modulates the cell cycle by regulating the Erk/Akt signaling pathway in lung adenocarcinoma. Thorac Cancer 2019; 10(4): 909-17.
[http://dx.doi.org/10.1111/1759-7714.13027] [PMID: 30838797]
[120]
Fukuda M. Regulation of secretory vesicle traffic by Rab small GTPases. Cell Mol Life Sci 2008; 65(18): 2801-13.
[http://dx.doi.org/10.1007/s00018-008-8351-4] [PMID: 18726178]
[121]
Yasuda T, Saegusa C, Kamakura S, Sumimoto H, Fukuda M. Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression. Mol Biol Cell 2012; 23(16): 3229-39.
[http://dx.doi.org/10.1091/mbc.e12-02-0104] [PMID: 22767581]
[122]
Hendrix A, Maynard D, Pauwels P, et al. Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis. J Natl Cancer Inst 2010; 102(12): 866-80.
[http://dx.doi.org/10.1093/jnci/djq153] [PMID: 20484105]
[123]
Ho JR, Chapeaublanc E, Kirkwood L, et al. Deregulation of Rab and Rab effector genes in bladder cancer. PLoS One 2012; 7(6): e39469.
[http://dx.doi.org/10.1371/journal.pone.0039469] [PMID: 22724020]
[124]
Ren P, Yang XQ, Zhai XL, Zhang YQ, Huang JF. Overexpression of Rab27B is correlated with distant metastasis and poor prognosis in ovarian cancer. Oncol Lett 2016; 12(2): 1539-45.
[http://dx.doi.org/10.3892/ol.2016.4801] [PMID: 27446467]
[125]
Zhang JX, Huang XX, Cai MB, et al. Overexpression of the secretory small GTPase Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis. J Transl Med 2012; 10: 242.
[http://dx.doi.org/10.1186/1479-5876-10-242] [PMID: 23217148]
[126]
Li J, Jin Q, Huang F, Tang Z, Huang J. Effects of Rab27A and Rab27B on invasion, proliferation, apoptosis, and chemoresistance in human pancreatic cancer cells. Pancreas 2017; 46(9): 1173-9.
[http://dx.doi.org/10.1097/MPA.0000000000000910] [PMID: 28902788]
[127]
Bao J, Ni Y, Qin H, et al. Rab27b is a potential predictor for metastasis and prognosis in colorectal cancer. Gastroenterol Res Pract 2014; 2014: 913106.
[http://dx.doi.org/10.1155/2014/913106] [PMID: 25580113]
[128]
Zhang L, Fan W, Xu L, et al. Rab27b Is a potential indicator for lymph node metastasis and unfavorable prognosis in lung adenocarcinoma. Dis Markers 2018; 2018: 7293962.
[http://dx.doi.org/10.1155/2018/7293962] [PMID: 30627227]
[129]
Nasrin N, Buggs C, Kong XF, Carnazza J, Goebl M, Alexander-Bridges M. DNA-binding properties of the product of the testis-determining gene and a related protein. Nature 1991; 354(6351): 317-20.
[http://dx.doi.org/10.1038/354317a0] [PMID: 1956382]
[130]
Gontan C, de Munck A, Vermeij M, Grosveld F, Tibboel D, Rottier R. Sox2 is important for two crucial processes in lung development: Branching morphogenesis and epithelial cell differentiation. Dev Biol 2008; 317(1): 296-309.
[http://dx.doi.org/10.1016/j.ydbio.2008.02.035] [PMID: 18374910]
[131]
Bass AJ, Watanabe H, Mermel CH, et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet 2009; 41(11): 1238-42.
[http://dx.doi.org/10.1038/ng.465] [PMID: 19801978]
[132]
Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 2012; 44(10): 1111-6.
[http://dx.doi.org/10.1038/ng.2405] [PMID: 22941189]
[133]
Nakatsugawa M, Takahashi A, Hirohashi Y, et al. SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma and augments the tumorigenicity. Lab Invest 2011; 91(12): 1796-804.
[http://dx.doi.org/10.1038/labinvest.2011.140] [PMID: 21931300]
[134]
Kim BR, Van de Laar E, Cabanero M, et al. SOX2 and PI3K cooperate to induce and stabilize a squamous-committed stem cell injury state during lung squamous cell carcinoma pathogenesis. PLoS Biol 2016; 14(11): e1002581.
[http://dx.doi.org/10.1371/journal.pbio.1002581] [PMID: 27880766]
[135]
Choe C, Kim H, Min S, Park S, Seo J, Roh S. SOX2, a stemness gene, induces progression of NSCLC A549 cells toward anchorage-independent growth and chemoresistance to vinblastine. OncoTargets Ther 2018; 11: 6197-207.
[http://dx.doi.org/10.2147/OTT.S175810] [PMID: 30288055]
[136]
Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251(5000): 1451-5.
[http://dx.doi.org/10.1126/science.2006419] [PMID: 2006419]
[137]
Chen T, Yuan D, Wei B, et al. E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. Stem Cells 2010; 28(8): 1315-25.
[http://dx.doi.org/10.1002/stem.456] [PMID: 20521328]
[138]
Redmer T, Diecke S, Grigoryan T, Quiroga-Negreira A, Birchmeier W, Besser D. E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO Rep 2011; 12(7): 720-6.
[http://dx.doi.org/10.1038/embor.2011.88] [PMID: 21617704]
[139]
Larue L, Antos C, Butz S, et al. A role for cadherins in tissue formation. Development 1996; 122(10): 3185-94.
[PMID: 8898231]
[140]
Karpowicz P, Willaime-Morawek S, Balenci L, DeVeale B, Inoue T, van der Kooy D. E-Cadherin regulates neural stem cell self-renewal. J Neurosci 2009; 29(12): 3885-96.
[http://dx.doi.org/10.1523/JNEUROSCI.0037-09.2009] [PMID: 19321785]
[141]
Li L, Wang S, Jezierski A, et al. A unique interplay between Rap1 and E-cadherin in the endocytic pathway regulates self-renewal of human embryonic stem cells. Stem Cells 2010; 28(2): 247-57.
[http://dx.doi.org/10.1002/stem.2925] [PMID: 20039365]
[142]
Li Z, Qiu D, Sridharan I, et al. Spatially resolved quantification of E-cadherin on target hES cells. J Phys Chem B 2010; 114(8): 2894-900.
[http://dx.doi.org/10.1021/jp906737q] [PMID: 20131884]
[143]
Rodriguez FJ, Lewis-Tuffin LJ, Anastasiadis PZ. E-cadherin’s dark side: Possible role in tumor progression. Biochim Biophys Acta 2012; 1826(1): 23-31.
[PMID: 22440943]
[144]
Berx G, Becker KF, Höfler H, van Roy F. Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 1998; 12(4): 226-37.
[http://dx.doi.org/10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D] [PMID: 9744472]
[145]
Machado JC, Soares P, Carneiro F, et al. E-cadherin gene mutations provide a genetic basis for the phenotypic divergence of mixed gastric carcinomas. Lab Invest 1999; 79(4): 459-65.
[PMID: 10211998]
[146]
Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev 2009; 28(1-2): 151-66.
[http://dx.doi.org/10.1007/s10555-008-9179-y] [PMID: 19153669]
[147]
Guilford P. E-cadherin downregulation in cancer: Fuel on the fire? Mol Med Today 1999; 5(4): 172-7.
[http://dx.doi.org/10.1016/S1357-4310(99)01461-6] [PMID: 10203750]
[148]
Stemmler MP. Cadherins in development and cancer. Mol Biosyst 2008; 4(8): 835-50.
[http://dx.doi.org/10.1039/b719215k] [PMID: 18633485]
[149]
Spaderna S, Schmalhofer O, Hlubek F, Jung A, Kirchner T, Brabletz T. Epithelial-mesenchymal and mesenchymal-epithelial transitions during cancer progression. Verh Dtsch Ges Pathol 2007; 91: 21-8.
[PMID: 18314592]
[150]
De Marzo AM, Knudsen B, Chan-Tack K, Epstein JI. E-cadherin expression as a marker of tumor aggressiveness in routinely processed radical prostatectomy specimens. Urology 1999; 53(4): 707-13.
[http://dx.doi.org/10.1016/S0090-4295(98)00577-9] [PMID: 10197845]
[151]
Chao YL, Shepard CR, Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer 2010; 9: 179.
[http://dx.doi.org/10.1186/1476-4598-9-179] [PMID: 20609236]
[152]
Ye T, Li J, Sun Z, et al. Cdh1 functions as an oncogene by inducing self-renewal of lung cancer stem-like cells via oncogenic pathways. Int J Biol Sci 2020; 16(3): 447-59.
[http://dx.doi.org/10.7150/ijbs.38672] [PMID: 32015681]
[153]
Jiang F, Ma S, Xue Y, Hou J, Zhang Y. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer. Biochem Biophys Res Commun 2016; 469(4): 985-92.
[http://dx.doi.org/10.1016/j.bbrc.2015.12.078] [PMID: 26721441]
[154]
Thonsri U, Seubwai W, Waraasawapati S, et al. Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated with poor prognosis. Histol Histopathol 2017; 32(5): 503-10.
[PMID: 27615379]
[155]
Huang X, Li X, Xie X, et al. High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer. Breast 2016; 30: 39-46.
[http://dx.doi.org/10.1016/j.breast.2016.08.014] [PMID: 27598996]
[156]
Hou XM, Yuan SQ, Zhao D, Liu XJ, Wu XA. LDH-A promotes malignant behavior via activation of epithelial-to-mesenchymal transition in lung adenocarcinoma. Biosci Rep 2019; 39(1): BSR20181476.
[http://dx.doi.org/10.1042/BSR20181476] [PMID: 30509961]

Rights & Permissions Print Cite
Article Metrics
25
© 2024 Bentham Science Publishers | Privacy Policy