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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

Cancer Stem Cells Equipped with Powerful Hedgehog Signaling and Better Epigenetic Memory: Avenues to Look for Cancer Therapeutics

Author(s): Ishita Tandon, Asawari Waghmode and Nilesh Kumar Sharma*

Volume 19, Issue 11, 2019

Page: [877 - 884] Pages: 8

DOI: 10.2174/1568009619666190808155432

Price: $65

Abstract

Complex nature of the tumor is depicted at the cellular landscape by showing heterogeneity in the presence of cancer cells, cancer-associated stromal cells, mesenchymal stem cells and cancer stem cells (CSCs). One of the plausible views in cancer formation is suggested as the theory of cancer CSCs that is known as a source of initiation of tumorigenesis. In essence, these powerful CSCs are equipped with high Sonic Hedgehog (SHH) signaling and epigenetic memory power that support various tumor hallmarks. Truly, nature justifies its intent by limiting these stem cells with a potential to turn into CSCs and in turn suppressing the high risk of humans and other organisms. In short, this mini-review addresses the contribution of SHH signaling to allow reprogramming of epigenetic memory within CSCs that support tumor hallmarks. Besides, this paper explores therapeutic approaches to mitigate SHH signaling that may lead to a blockade of the pro-tumor potential of CSCs.

Keywords: CSCs, epigenome, genome, inhibitors, neoplasm, sonic hedgehog signaling, therapeutics.

Graphical Abstract

[1]
Shibue, T.; Weinberg, R.A. EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat. Rev. Clin. Oncol., 2017, 14(10), 611-629.
[http://dx.doi.org/10.1038/nrclinonc.2017.44] [PMID: 28397828]
[2]
Eun, K.; Ham, S.W.; Kim, H. Cancer stem cell heterogeneity: Origin and new perspectives on CSC targeting. BMB Rep., 2017, 50(3), 117-125.
[http://dx.doi.org/10.5483/BMBRep.2017.50.3.222] [PMID: 27998397]
[3]
Prasetyanti, P.R.; Medema, J.P. Intra-tumor heterogeneity from a cancer stem cell perspective. Mol. Cancer, 2017, 16(1), 41.
[http://dx.doi.org/10.1186/s12943-017-0600-4] [PMID: 28209166]
[4]
Tandon, I.; Sharma, N.K. Macrophage flipping from foe to friend: A matter of interest in breast carcinoma heterogeneity driving drug resistance. Curr. Cancer Drug Targets, 2019, 19(3), 189-198.
[http://dx.doi.org/10.2174/1568009618666180628102247] [PMID: 29952260]
[5]
Liu, X.; Zhao, T.; Bai, X.; Li, M.; Ren, J.; Wang, M.; Xu, R.; Zhang, S.; Li, H.; Hu, Y.; Xie, L.; Zhang, Y.; Yang, L.; Yan, C.; Zhang, Y. LOC101930370/MiR-1471 Axis modulates the hedgehog signaling pathway in breast cancer. Cell. Physiol. Biochem., 2018, 48(3), 1139-1150.
[http://dx.doi.org/10.1159/000491980] [PMID: 30041193]
[6]
Nilendu, P.; Sarode, S.C.; Jahagirdar, D.; Tandon, I.; Patil, S.; Sarode, G.S.; Pal, J.K.; Sharma, N.K. Mutual concessions and compromises between stromal cells and cancer cells: Driving tumor development and drug resistance. Cell Oncol. (Dordr.), 2018, 41(4), 353-367.
[http://dx.doi.org/10.1007/s13402-018-0388-2] [PMID: 30027403]
[7]
Hernandez, A.L.; Wang, Y.; Somerset, H.L.; Keysar, S.B.; Aisner, D.L.; Marshall, C.; Bowles, D.W.; Karam, S.D.; Raben, D.; Jimeno, A.; Varella-Garcia, M.; Wang, X.J. Inter and intra-tumor heterogeneity of SMAD4 loss in head and neck squamous cell carcinoma. Mol. Carcinog., 2018, 25, 117-426.
[8]
Devashree, J. Shruti, Purohit.; Aayushi, Jain.; Sharma, N.K. Export of short RNAs: A bridge between breast carcinoma and their neighboring cells. Front. Oncol., 2016, 6, 147.
[9]
Ajani, J.A.; Song, S.; Hochster, H.S.; Steinberg, I.B. Cancer stem cells: The promise and the potential. Semin. Oncol., 2015, 42(Suppl. 1), S3-S17.
[http://dx.doi.org/10.1053/j.seminoncol.2015.01.001] [PMID: 25839664]
[10]
Takebe, N.; Miele, L.; Harris, P.J.; Jeong, W.; Bando, H.; Kahn, M.; Yang, S.X.; Ivy, S.P. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat. Rev. Clin. Oncol., 2015, 12(8), 445-464.
[http://dx.doi.org/10.1038/nrclinonc.2015.61] [PMID: 25850553]
[11]
Tanaka, S. Cancer stem cells as therapeutic targets of hepato-biliary-pancreatic cancers. J. Hepatobiliary Pancreat. Sci., 2015, 22(7), 531-537.
[http://dx.doi.org/10.1002/jhbp.248] [PMID: 25874410]
[12]
Lynch, J.; Wang, J.Y. G protein-coupled receptor signaling in stem cells and cancer 2016, 11,17(5)
[http://dx.doi.org/10.3390/ijms17050707]
[13]
Pires, B.; Amorim, Í.; Souza, L.; Rodrigues, J.; Mencalha, A. Targeting Cellular Signaling Pathways in Breast CSCs and its Implication for Cancer Treatment, 2016, 13(11), 5681-5691.
[14]
Wainwright, E.N.; Scaffidi, P. Epigenetics and cancer stem cells: Unleashing, hijacking, and restricting cellular plasticity. Trends Cancer, 2017, 3(5), 372-386.
[http://dx.doi.org/10.1016/j.trecan.2017.04.004] [PMID: 28718414]
[15]
Yan, Y.; Wang, Y.; Zhao, P.; Ma, W.; Hu, Z.; Zhang, K. BMI-1 Promotes self-renewal of radio- and temozolomide (TMZ)-resistant breast cancer cells. Reprod. Sci., 2017, 24(12), 1620-1629.
[http://dx.doi.org/10.1177/1933719117697255] [PMID: 28270035]
[16]
Neumann, J.E.; Wefers, A.K.; Lambo, S.; Bianchi, E.; Bockstaller, M.; Dorostkar, M.M.; Meister, V.; Schindler, P.; Korshunov, A.; von Hoff, K.; Nowak, J.; Warmuth-Metz, M.; Schneider, M.R.; Renner-Müller, I.; Merk, D.J.; Shakarami, M.; Sharma, T.; Chavez, L.; Glass, R.; Chan, J.A.; Taketo, M.M.; Neumann, P.; Kool, M.; Schüller, U. A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors. Nat. Med., 2017, 23(10), 1191-1202.
[http://dx.doi.org/10.1038/nm.4402] [PMID: 28892064]
[17]
Cazet, A.S.; Hui, M.N.; Elsworth, B.L.; Wu, S.Z.; Roden, D.; Chan, C.L.; Skhinas, J.N.; Collot, R.; Yang, J.; Harvey, K.; Johan, M.Z.; Cooper, C.; Nair, R.; Herrmann, D.; McFarland, A.; Deng, N.; Ruiz-Borrego, M.; Rojo, F.; Trigo, J.M.; Bezares, S.; Caballero, R.; Lim, E.; Timpson, P.; O’Toole, S.; Watkins, D.N.; Cox, T.R.; Samuel, M.S.; Martín, M.; Swarbrick, A. Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer. Nat. Commun., 2018, 9(1), 2897.
[http://dx.doi.org/10.1038/s41467-018-05220-6] [PMID: 30042390]
[18]
Lathia, J.D.; Liu, H. Overview of cancer stem cells and stemness for community oncologists. Target. Oncol., 2017, 12(4), 387-399.
[http://dx.doi.org/10.1007/s11523-017-0508-3] [PMID: 28664387]
[19]
Regan, J.L.; Schumacher, D.; Staudte, S.; Steffen, A.; Haybaeck, J.; Keilholz, U.; Schweiger, C.; Golob-Schwarzl, N.; Mumberg, D.; Henderson, D.; Lehrach, H.; Regenbrecht, C.R.A.; Schäfer, R.; Lange, M. Non-canonical hedgehog signaling is a positive regulator of the WNT pathway and is required for the survival of colon cancer stem cells. Cell Rep., 2017, 21(10), 2813-2828.
[http://dx.doi.org/10.1016/j.celrep.2017.11.025] [PMID: 29212028]
[20]
Valenti, G.; Quinn, H.M.; Heynen, G.J.J.E.; Lan, L.; Holland, J.D.; Vogel, R.; Wulf-Goldenberg, A.; Birchmeier, W. Cancer stem cells regulate cancer-associated fibroblasts via activation of hedgehog signaling in mammary gland tumors. Cancer Res., 2017, 77(8), 2134-2147.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3490] [PMID: 28202523]
[21]
Deshmukh, A.; Binju, M.; Arfuso, F.; Newsholme, P.; Dharmarajan, A. Role of epigenetic modulation in cancer stem cell fate. Int. J. Biochem. Cell Biol., 2017, 90, 9-16.
[http://dx.doi.org/10.1016/j.biocel.2017.07.003] [PMID: 28711634]
[22]
Yang, Z.; Zhang, C.; Qi, W.; Cui, Y.; Xuan, Y. GLI1 promotes cancer stemness through intracellular signaling pathway PI3K/Akt/NFκB in colorectal adenocarcinoma. Exp. Cell Res., 2018, 373(1-2), 145-154.
[http://dx.doi.org/10.1016/j.yexcr.2018.10.006] [PMID: 30321514]
[23]
Di Magno, L.; Coni, S.; Di Marcotullio, L.; Canettieri, G. Digging a hole under Hedgehog: Downstream inhibition as an emerging anticancer strategy. Biochim. Biophys. Acta, 2015, 1856(1), 62-72.
[PMID: 26080084]
[24]
Della Corte, C.M.; Viscardi, G.; Papaccio, F.; Esposito, G.; Martini, G.; Ciardiello, D.; Martinelli, E.; Ciardiello, F.; Morgillo, F. Implication of the hedgehog pathway in hepatocellular carcinoma. World J. Gastroenterol., 2017, 23(24), 4330-4340.
[http://dx.doi.org/10.3748/wjg.v23.i24.4330] [PMID: 28706416]
[25]
Infante, P.; Faedda, R.; Bernardi, F.; Bufalieri, F.; Lospinoso Severini, L.; Alfonsi, R.; Mazzà, D.; Siler, M.; Coni, S.; Po, A.; Petroni, M.; Ferretti, E.; Mori, M.; De Smaele, E.; Canettieri, G.; Capalbo, C.; Maroder, M.; Screpanti, I.; Kool, M.; Pfister, S.M.; Guardavaccaro, D.; Gulino, A.; Di Marcotullio, L. Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis. Nat. Commun., 2018, 9(1), 976.
[http://dx.doi.org/10.1038/s41467-018-03339-0] [PMID: 29515120]
[26]
Huang, D.; Wang, Y.; Tang, J.; Luo, S. Molecular mechanisms of suppressor of fused in regulating the hedgehog signalling pathway. Oncol. Lett., 2018, 15(5), 6077-6086.
[http://dx.doi.org/10.3892/ol.2018.8142] [PMID: 29725392]
[27]
Tang, Y.; Gholamin, S.; Schubert, S.; Willardson, M.I.; Lee, A.; Bandopadhayay, P.; Bergthold, G.; Masoud, S.; Nguyen, B.; Vue, N.; Balansay, B.; Yu, F.; Oh, S.; Woo, P.; Chen, S.; Ponnuswami, A.; Monje, M.; Atwood, S.X.; Whitson, R.J.; Mitra, S.; Cheshier, S.H.; Qi, J.; Beroukhim, R.; Tang, J.Y.; Wechsler-Reya, R.; Oro, A.E.; Link, B.A.; Bradner, J.E.; Cho, Y.J. Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat. Med., 2014, 20(7), 732-740.
[http://dx.doi.org/10.1038/nm.3613] [PMID: 24973920]
[28]
Lin, J.; Tan, H.; Nie, Y.; Wu, D.; Zheng, W.; Lin, W.; Zhu, Z.; Yang, B.; Chen, X.; Chen, T. Krüppel-like factor 2 inhibits hepatocarcinogenesis through negative regulation of the Hedgehog pathway. Cancer Sci., 2019, 110(4), 1220-1231.
[http://dx.doi.org/10.1111/cas.13961] [PMID: 30719823]
[29]
Shi, X.; Zhang, Z.; Zhan, X.; Cao, M.; Satoh, T.; Akira, S.; Shpargel, K.; Magnuson, T.; Li, Q.; Wang, R.; Wang, C.; Ge, K.; Wu, J. An epigenetic switch induced by Shh signalling regulates gene activation during development and medulloblastoma growth. Nat. Commun., 2014, 5, 5425.
[http://dx.doi.org/10.1038/ncomms6425] [PMID: 25370275]
[30]
Malatesta, M.; Steinhauer, C.; Mohammad, F.; Pandey, D.P.; Squatrito, M.; Helin, K. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation. Cancer Res., 2013, 73(20), 6323-6333.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-4660] [PMID: 23943798]
[31]
Tang, Y.A.; Chen, Y.F.; Bao, Y.; Mahara, S.; Yatim, S.M.J.M.; Oguz, G.; Lee, P.L.; Feng, M.; Cai, Y.; Tan, E.Y.; Fong, S.S.; Yang, Z.H.; Lan, P.; Wu, X.J.; Yu, Q. Hypoxic tumor microenvironment activates GLI2 via HIF-1α and TGF-β2 to promote chemoresistance in colorectal cancer. Proc. Natl. Acad. Sci. USA, 2018, 115(26), E5990-E5999.
[http://dx.doi.org/10.1073/pnas.1801348115] [PMID: 29891662]
[32]
Bora-Singhal, N.; Perumal, D.; Nguyen, J.; Chellappan, S. Gli1-mediated regulation of Sox2 facilitates self-renewal of stem-like cells and confers resistance to EGFR inhibitors in non-small cell lung cancer. Neoplasia, 2015, 17(7), 538-551.
[http://dx.doi.org/10.1016/j.neo.2015.07.001] [PMID: 26297432]
[33]
Aval, S.F.; Lotfi, H.; Sheervalilou, R.; Zarghami, N. Tuning of major signaling networks (TGF-β, Wnt, Notch and Hedgehog) by miRNAs in human stem cells commitment to different lineages: Possible clinical application. Biomed. Pharmacother., 2017, 91, 849-860.
[http://dx.doi.org/10.1016/j.biopha.2017.05.020] [PMID: 28501774]
[34]
Miele, E.; Po, A.; Begalli, F.; Antonucci, L.; Mastronuzzi, A.; Marras, C.E.; Carai, A.; Cucchi, D.; Abballe, L.; Besharat, Z.M.; Catanzaro, G.; Infante, P.; Di Marcotullio, L.; Canettieri, G.; De Smaele, E.; Screpanti, I.; Locatelli, F.; Ferretti, E. β-arrestin1-mediated acetylation of Gli1 regulates Hedgehog/Gli signaling and modulates self-renewal of SHH medulloblastoma cancer stem cells. BMC Cancer, 2017, 17(1), 488.
[http://dx.doi.org/10.1186/s12885-017-3477-0] [PMID: 28716052]
[35]
Levanat, S.; Sabol, M.; Musani, V.; Ozretic, P.; Trnski, D. Hedgehog signaling pathway as genetic and epigenetic target in ovarian tumors. Curr. Pharm. Des., 2017, 23(1), 73-94.
[PMID: 27719639]
[36]
Samadani, A.A.; Norollahi, S.E.; Rashidy-Pour, A.; Mansour-Ghanaei, F.; Nemati, S.; Joukar, F.; Afshar, A.M.; Ghazanfari, S.; Safizadeh, M.; Rostami, P.; Gatei, M. Cancer signaling pathways with a therapeutic approach: An overview in epigenetic regulations of cancer stem cells. Biomed. Pharmacother., 2018, 108, 590-599.
[http://dx.doi.org/10.1016/j.biopha.2018.09.048] [PMID: 30243093]
[37]
Fattahi, S.; Pilehchian Langroudi, M.; Akhavan-Niaki, H. Hedgehog signaling pathway: Epigenetic regulation and role in disease and cancer development. J. Cell. Physiol., 2018, 233(8), 5726-5735.
[http://dx.doi.org/10.1002/jcp.26506] [PMID: 29380372]
[38]
Wu, J.; Zhu, P.; Lu, T.; Du, Y.; Wang, Y.; He, L.; Ye, B.; Liu, B.; Yang, L.; Wang, J.; Gu, Y.; Lan, J.; Hao, Y.; He, L.; Fan, Z. The long noncoding RNA LncHDAC2 drives the self-renewal of liver CSCs via activation of Hedgehog Signaling. J. Hepatol., 2018, 45, 653-662.
[39]
Katoh, M. Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers. Clin. Sci. (Lond.), 2019, 133(8), 953-970.
[http://dx.doi.org/10.1042/CS20180845] [PMID: 31036756]
[40]
Kim, S.; Kim, Y.; Kong, J.; Kim, E.; Choi, J.H.; Yuk, H.D.; Lee, H.; Kim, H.R.; Lee, K.H.; Kang, M.; Roe, J.S.; Moon, K.C.; Kim, S.; Ku, J.H.; Shin, K. Epigenetic regulation of mammalian Hedgehog signaling to the stroma determines the molecular subtype of bladder cancer. eLife, 2019. 8e43024
[http://dx.doi.org/10.7554/eLife.43024] [PMID: 31036156]
[41]
Rallis, G.; Koletsa, T.; Saridaki, Z.; Manousou, K.; Koliou, G.A.; Kostopoulos, I.; Kotoula, V.; Makatsoris, T.; Kourea, H.P.; Raptou, G.; Chrisafi, S.; Samantas, E.; Papaparaskeva, K.; Pazarli, E.; Papakostas, P.; Kafiri, G.; Mauri, D.; Papoudou-Bai, A.; Christodoulou, C.; Petraki, K.; Dombros, N.; Pectasides, D.; Fountzilas, G. Association of notch and hedgehog pathway activation with prognosis in early-stage colorectal cancer. Anticancer Res., 2019, 39(4), 2129-2138.
[http://dx.doi.org/10.21873/anticanres.13326] [PMID: 30952759]
[42]
Riaz, S.K.; Ke, Y.; Wang, F.; Kayani, M.A.; Malik, M.F.A. Influence of SHH/GLI1 axis on EMT mediated migration and invasion of breast cancer cells. Sci. Rep., 2019, 9(1), 6620.
[http://dx.doi.org/10.1038/s41598-019-43093-x] [PMID: 31036836]
[43]
Taylor, R.; Long, J.; Yoon, J.W.; Childs, R.; Sylvestersen, K.B.; Nielsen, M.L.; Leong, K.F.; Iannaccone, S.; Walterhouse, D.O.; Robbins, D.J.; Iannaccone, P. Regulation of GLI1 by cis DNA elements and epigenetic marks. DNA Repair (Amst.), 2019, 79, 10-21.
[http://dx.doi.org/10.1016/j.dnarep.2019.04.011] [PMID: 31085420]
[44]
Katoh, Y.; Katoh, M. WNT antagonist, SFRP1, is Hedgehog signaling target. Int. J. Mol. Med., 2006, 17(1), 171-175.
[http://dx.doi.org/10.3892/ijmm.17.1.171] [PMID: 16328026]
[45]
Chun, S.G.; Zhou, W.; Yee, N.S. Combined targeting of histone deacetylases and hedgehog signaling enhances cytoxicity in pancreatic cancer. Cancer Biol. Ther., 2009, 8(14), 1328-1339.
[http://dx.doi.org/10.4161/cbt.8.14.8633] [PMID: 19421011]
[46]
Chun, S.G.; Park, H.; Pandita, R.K.; Horikoshi, N.; Pandita, T.K.; Schwartz, D.L.; Yordy, J.S. Targeted inhibition of histone deacetylases and hedgehog signaling suppress tumor growth and homologous recombination in aerodigestive cancers. Am. J. Cancer Res., 2015, 5(4), 1337-1352.
[PMID: 26101701]
[47]
Zuo, M.; Rashid, A.; Churi, C.; Vauthey, J.N.; Chang, P.; Li, Y.; Hung, M.C.; Li, D.; Javle, M. Novel therapeutic strategy targeting the Hedgehog signalling and mTOR pathways in biliary tract cancer. Br. J. Cancer, 2015, 112(6), 1042-1051.
[http://dx.doi.org/10.1038/bjc.2014.625] [PMID: 25742482]
[48]
Benvenuto, M.; Masuelli, L.; De Smaele, E.; Fantini, M.; Mattera, R.; Cucchi, D.; Bonanno, E.; Di Stefano, E.; Frajese, G.V.; Orlandi, A.; Screpanti, I.; Gulino, A.; Modesti, A.; Bei, R. In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors. Oncotarget, 2016, 7(8), 9250-9270.
[http://dx.doi.org/10.18632/oncotarget.7062] [PMID: 26843616]
[49]
Koike, Y.; Ohta, Y.; Saitoh, W.; Yamashita, T.; Kanomata, N.; Moriya, T.; Kurebayashi, J. Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 in triple-negative breast cancer cells. Breast Cancer, 2017, 24(5), 683-693.
[http://dx.doi.org/10.1007/s12282-017-0757-0] [PMID: 28144905]
[50]
Paluszczak, J.; Wiśniewska, D.; Kostrzewska-Poczekaj, M.; Kiwerska, K.; Grénman, R.; Mielcarek-Kuchta, D.; Jarmuż-Szymczak, M. Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas. Clin. Oral Investig., 2017, 21(5), 1777-1788.
[http://dx.doi.org/10.1007/s00784-016-1946-5] [PMID: 27553089]
[51]
Fareh, M.; Turchi, L.; Virolle, V.; Debruyne, D.; Almairac, F.; de-la-Forest Divonne, S.; Paquis, P.; Preynat-Seauve, O.; Krause, K.H.; Chneiweiss, H.; Virolle, T. The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network. Cell Death Differ., 2012, 19(2), 232-244.
[http://dx.doi.org/10.1038/cdd.2011.89] [PMID: 21720384]
[52]
Ahmad, A.; Maitah, M.Y.; Ginnebaugh, K.R.; Li, Y.; Bao, B.; Gadgeel, S.M.; Sarkar, F.H. Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs. J. Hematol. Oncol., 2013, 6(1), 77.
[http://dx.doi.org/10.1186/1756-8722-6-77] [PMID: 24199791]
[53]
Yu, F.; Zheng, Y.; Hong, W.; Chen, B.; Dong, P.; Zheng, J. MicroRNA-200a suppresses epithelial-to-mesenchymal transition in rat hepatic stellate cells via GLI family zinc finger 2. Mol. Med. Rep., 2015, 12(6), 8121-8128.
[http://dx.doi.org/10.3892/mmr.2015.4452] [PMID: 26499180]
[54]
Xu, L.; Liu, H.; Yan, Z.; Sun, Z.; Luo, S.; Lu, Q. Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells. Int. J. Oncol., 2017, 50(5), 1868-1878.
[http://dx.doi.org/10.3892/ijo.2017.3946] [PMID: 28393219]
[55]
Besharat, Z.M.; Abballe, L.; Cicconardi, F.; Bhutkar, A.; Grassi, L.; Le Pera, L.; Moretti, M.; Chinappi, M.; D’Andrea, D.; Mastronuzzi, A.; Ianari, A.; Vacca, A.; De Smaele, E.; Locatelli, F.; Po, A.; Miele, E.; Ferretti, E. Foxm1 controls a pro-stemness microRNA network in neural stem cells. Sci. Rep., 2018, 8(1), 3523.
[http://dx.doi.org/10.1038/s41598-018-21876-y] [PMID: 29476172]
[56]
Kim, J.; Hyun, J.; Wang, S.; Lee, C.; Jung, Y. MicroRNA-378 is involved in hedgehog-driven epithelial-to-mesenchymal transition in hepatocytes of regenerating liver. Cell Death Dis., 2018, 9(7), 721.
[http://dx.doi.org/10.1038/s41419-018-0762-z] [PMID: 29915286]
[57]
Long, J.; Li, B.; Rodriguez-Blanco, J.; Pastori, C.; Volmar, C.H.; Wahlestedt, C.; Capobianco, A.; Bai, F.; Pei, X.H.; Ayad, N.G.; Robbins, D.J. The BET bromodomain inhibitor I-BET151 acts downstream of smoothened protein to abrogate the growth of hedgehog protein-driven cancers. J. Biol. Chem., 2014, 289(51), 35494-35502.
[http://dx.doi.org/10.1074/jbc.M114.595348] [PMID: 25355313]
[58]
Armas-López, L.; Piña-Sánchez, P.; Arrieta, O.; de Alba, E.G.; Ortiz-Quintero, B.; Santillán-Doherty, P.; Christiani, D.C.; Zúñiga, J.; Ávila-Moreno, F. Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients. Oncotarget, 2017, 8(40), 67056-67081.
[http://dx.doi.org/10.18632/oncotarget.17715] [PMID: 28978016]
[59]
Pignot, G.; Vieillefond, A.; Vacher, S.; Zerbib, M.; Debre, B.; Lidereau, R.; Amsellem-Ouazana, D.; Bieche, I. Hedgehog pathway activation in human transitional cell carcinoma of the bladder. Br. J. Cancer, 2012, 106(6), 1177-1186.
[http://dx.doi.org/10.1038/bjc.2012.55] [PMID: 22361633]
[60]
Raven, P.A.; Lysakowski, S.; Tan, Z.; D’Costa, N.M.; Moskalev, I.; Frees, S.; Struss, W.; Matsui, Y.; Narita, S.; Buttyan, R.; Chavez-Munoz, C.; So, A.I. Inhibition of GLI2 with antisense-oligonucleotides: A potential therapy for the treatment of bladder cancer. J. Cell. Physiol., 2019, 234(11), 20634-20647.
[http://dx.doi.org/10.1002/jcp.28669] [PMID: 31012113]
[61]
Ma, H.; Chen, Q.; Zhu, F.; Zheng, J.; Li, J.; Zhang, H.; Chen, S.; Xing, H.; Luo, L.; Zheng, L.T.; He, S.; Zhang, X. Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor. Eur. J. Med. Chem., 2018, 149, 110-121.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.034] [PMID: 29499483]
[62]
Abidi, A. Hedgehog signaling pathway: a novel target for cancer therapy: Vismodegib, a promising therapeutic option in treatment of basal cell carcinomas. Indian J. Pharmacol., 2014, 46(1), 3-12.
[http://dx.doi.org/10.4103/0253-7613.124884] [PMID: 24550577]
[63]
Zhang, M.; Tan, S.; Yu, D.; Zhao, Z.; Zhang, B.; Zhang, P.; Lv, C.; Zhou, Q.; Cao, Z. Triptonide inhibits lung cancer cell tumorigenicity by selectively attenuating the Shh-Gli1 signaling pathway. Toxicol. Appl. Pharmacol., 2019, 365, 1-8.
[http://dx.doi.org/10.1016/j.taap.2019.01.002] [PMID: 30610878]
[64]
Melamed, J.R.; Ioele, S.A.; Hannum, A.J.; Ullman, V.M.; Day, E.S. Polyethylenimine-spherical nucleic acid nanoparticles against gli1 reduce the chemoresistance and stemness of glioblastoma cells. Mol. Pharm., 2018, 15(11), 5135-5145.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00707] [PMID: 30260647]
[65]
Yang, W.; Liu, Y.; Gao, R.; Yu, H.; Sun, T. HDAC6 inhibition induces glioma stem cells differentiation and enhances cellular radiation sensitivity through the SHH/Gli1 signaling pathway. Cancer Lett., 2018, 415, 164-176.
[http://dx.doi.org/10.1016/j.canlet.2017.12.005] [PMID: 29222038]
[66]
Krauss, S.; Foerster, J.; Schneider, R.; Schweiger, S. Protein phosphatase 2A and rapamycin regulate the nuclear localization and activity of the transcription factor GLI3. Cancer Res., 2008, 68(12), 4658-4665.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6174] [PMID: 18559511]

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