Login Register Cart 0
Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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

Sox2: A Regulatory Factor in Tumorigenesis and Metastasis

Author(s): Sameer Chaudhary*, Zeyaul Islam, Vijaya Mishra, Sakshi Rawat, Ghulam Md. Ashraf* and Prasanna R. Kolatkar*

Volume 20, Issue 6, 2019

Page: [495 - 504] Pages: 10

DOI: 10.2174/1389203720666190325102255

Price: $65

Abstract

The transcription factor Sox2 plays an important role in various phases of embryonic development, including cell fate and differentiation. These key regulatory functions are facilitated by binding to specific DNA sequences in combination with partner proteins to exert their effects. Recently, overexpression and gene amplification of Sox2 has been associated with tumor aggression and metastasis in various cancer types, including breast, prostate, lung, ovarian and colon cancer. All the different roles for Sox2 involve complicated regulatory networks consisting of protein-protein and protein-nucleic acid interactions. Their involvement in the EMT modulation is possibly enabled by Wnt/ β-catenin and other signaling pathways. There are number of in vivo models which show Sox2 association with increased cancer aggressiveness, resistance to chemo-radiation therapy and decreased survival rate suggesting Sox2 as a therapeutic target. This review will focus on the different roles for Sox2 in metastasis and tumorigenesis. We will also review the mechanism of action underlying the cooperative Sox2- DNA/partner factors binding where Sox2 can be potentially explored for a therapeutic opportunity to treat cancers.

Keywords: HMG domain, endodermal-mesenchymal transition, transcription factor, tumor propagation, metastasis, overexpression, Wnt/β-catonin.

« Previous Next »
Graphical Abstract

[1]
Bowles, J.; Schepers, G.; Koopman, P. Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. Dev. Biol., 2000, 227, 239-255.
[2]
Harley, V.R.; Lovell-badge, R.; Goodfellow, P.N. Definition of a consensus DNA binding site for SRY. Nucleic Acids Res., 1994, 22, 1500-1501.
[3]
Lovell-Badge, R. The early history of the sox genes. Int. J. Biochem. Cell Biol., 2010, 42, 378-380.
[4]
Hawkins, K.; Joy, S.; McKay, T. Cell signalling pathways underlying induced pluripotent stem cell reprogramming. World J. Stem Cells, 2014, 6, 620-628.
[5]
Graham, V.; Khudyakov, J.; Ellis, P.; Pevny, L. SOX2 functions to maintain neural progenitor identity. Neuron, 2003, 39, 749-765.
[6]
Basu-Roy, U.; Ambrosetti, D.; Favaro, R.; Nicolis, S.K.; Mansukhani, A.; Basilico, C. The transcription factor Sox2 is required for osteoblast self-renewal. Cell Death Differ., 2010, 17, 1345-1353.
[7]
Zhang, S. Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J. Stem Cells, 2014, 6, 305.
[8]
Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 2007, 131, 861-872.
[9]
Ichida, J.K.; Blanchard, J.; Lam, K.; Son, E.Y.; Chung, J.E.; Egli, D.; Loh, K.M.; Carter, A.C.; Di Giorgio, F.P.; Koszka, K.; Huangfu, D.; Akutsu, H.; Liu, D.R.; Rubin, L.L.; Eggan, K. A small-molecule inhibitor of Tgf-β signaling replaces Sox2 in reprogramming by inducing nanog. Cell Stem Cell, 2009, 5, 491-503.
[10]
Zoumaro-Djayoon, A.D.; Ding, V.; Foong, L.Y.; Choo, A.; Heck, A.J.R.; Muñoz, J. Investigating the role of FGF-2 in stem cell maintenance by global phosphoproteomics profiling. Proteomics, 2011, 11, 3962-3971.
[11]
Lundberg, I.V.; Edin, S.; Eklöf, V.; Öberg, Å.; Palmqvist, R.; Wikberg, M.L. SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2 in colorectal cancer. BMC Cancer, 2016, 16, 471.
[12]
Justilien, V.; Walsh, M.P.; Ali, S.A.; Thompson, E.A.; Murray, N.R.; Fields, A.P. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate hedgehog signaling in lung squamous cell carcinoma. Cancer Cell, 2014, 25, 139-151.
[13]
Hussenet, T.; Dali, S.; Exinger, J.; Monga, B.; Jost, B.; Dembelé, D.; Martinet, N.; Thibault, C.; Huelsken, J.; Brambilla, E.; Du Manoir, S. SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One, 2010, 5, e8960.
[14]
McCaughan, F.; Pole, J.C.M.; Bankier, A.T.; Konfortov, B.A.; Carroll, B.; Falzon, M.; Rabbitts, T.H.; George, P.J.; Dear, P.H.; Rabbitts, P.H. Progressive 3q amplification consistently targets SOX2 in preinvasive squamous lung cancer. Am. J. Respir. Crit. Care Med., 2010, 182, 83-91.
[15]
Wilbertz, T.; Wagner, P.; Petersen, K.; Stiedl, A-C.; Scheble, V.J.; Maier, S.; Reischl, M.; Mikut, R.; Altorki, N.K.; Moch, H.; Fend, F.; Staebler, A.; Bass, A.J.; Meyerson, M.; Rubin, M. a; Soltermann, A.; Lengerke, C.; Perner, S. SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer. Mod. Pathol., 2011, 24, 944-953.
[16]
Saigusa, S.; Tanaka, K.; Toiyama, Y.; Yokoe, T.; Okugawa, Y.; Ioue, Y.; Miki, C.; Kusunoki, M. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann. Surg. Oncol., 2009, 16, 3488-3498.
[17]
Li, X.; Wang, J.; Xu, Z.; Ahmad, A.; Li, E.; Wang, Y.; Qin, S.; Wang, Q. Expression of Sox2 and Oct4 and their clinical significance in human non-small-cell lung cancer. Int. J. Mol. Sci., 2012, 13, 7663-7675.
[18]
Lu, Y.; Futtner, C.; Rock, J.R.; Xu, X.; Whitworth, W.; Hogan, B.L.M.; Onaitis, M.W. Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One, 2010, 5, e11022.
[19]
Xu, N.; Papagiannakopoulos, T.; Pan, G.; Thomson, J.A.; Kosik, K.S. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell, 2009, 137, 647-658.
[20]
Peng, C.; Li, N.; Ng, Y-K.; Zhang, J.; Meier, F.; Theis, F.J.; Merkenschlager, M.; Chen, W.; Wurst, W.; Prakash, N. A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. J. Neurosci., 2012, 32, 13292-13308.
[21]
Jeong, C.H.; Cho, Y.Y.; Kim, M.O.; Kim, S.H.; Cho, E.J.; Lee, S.Y.; Jeon, Y.J.; Lee, K.Y.; Yao, K.; Keum, Y.S.; Bode, A.M.; Dong, Z. Phosphorylation of Sox2 cooperates in reprogramming to pluripotent stem cells. Stem Cells, 2010, 28, 2141-2150.
[22]
Van Hoof, D.; Muñoz, J.; Braam, S.R.; Pinkse, M.W.H.; Linding, R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J. Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell, 2009, 5, 214-226.
[23]
Tsuruzoe, S.; Ishihara, K.; Uchimura, Y.; Watanabe, S.; Sekita, Y.; Aoto, T.; Saitoh, H.; Yuasa, Y.; Niwa, H.; Kawasuji, M.; Baba, H.; Nakao, M. Inhibition of DNA binding of Sox2 by the SUMO conjugation. Biochem. Biophys. Res. Commun., 2006, 351, 920-926.
[24]
Baltus, G.A.; Kowalski, M.P.; Zhai, H.; Tutter, A.V.; Quinn, D.; Wall, D.; Kadam, S. Acetylation of Sox2 induces its nuclear export in embryonic stem cells. Stem Cells, 2009, 27, 2175-2184.
[25]
Zhao, H.; Zhang, Y.J.; Dai, H.; Zhang, Y.; Shen, Y.F. CARM1 mediates modulation of Sox2. PLoS One, 2011, 6, e27026.
[26]
Jang, H.; Kim, T.W.; Yoon, S.; Choi, S.Y.; Kang, T.W.; Kim, S.Y.; Kwon, Y.W.; Cho, E.J.; Youn, H.D. O-GlcNAc regulates pluripotency and reprogramming by directly acting on core components of the pluripotency network. Cell Stem Cell, 2012, 11, 62-74.
[27]
Myers, S.A.; Peddada, S.; Chatterjee, N.; Friedrich, T.; Tomoda, K.; Krings, G.; Thomas, S.; Maynard, J.; Broeker, M.; Thomson, M.; Pollard, K.; Yamanaka, S.; Burlingame, A.L.; Panning, B. SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells. eLife, 2016, 5, e10647.
[28]
Fang, L.; Zhang, L.; Wei, W.; Jin, X.; Wang, P.; Tong, Y.; Li, J.; Du, J.X.; Wong, J. A Methylation-phosphorylation switch determines SOX2 stability and function in ESC maintenance or differentiation. Mol. Cell, 2014, 55, 537-551.
[29]
Kamachi, Y.; Uchikawa, M.; Collignon, J.; Lovell-Badge, R.; Kondoh, H. Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Development, 1998, 125, 2521-2532.
[30]
Reményi, A.; Lins, K.; Nissen, L.J.; Reinbold, R.; Schöler, H.R.; Wilmanns, M. Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev., 2003, 17, 2048-2059.
[31]
Werner, M.H.; Huth, J.R.; Gronenborn, A.M.; Marius Clore, G. Molecular basis of human 46X, Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex. Cell, 1995, 81, 705-714.
[32]
Williams, D.C.; Cai, M.; Clore, G.M. Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1·Sox2· Hoxb1-DNA ternary transcription factor complex. J. Biol. Chem., 2004, 279, 1449-1457.
[33]
Kamachi, Y.; Uchikawa, M.; Kondoh, H. Pairing SOX off: With partners in the regulation of embryonic development. Trends Genet., 2000, 16, 182-187.
[34]
Seo, E.; Basu-Roy, U.; Zavadil, J.; Basilico, C.; Mansukhani, A. Distinct functions of Sox2 control self-renewal and differentiation in the osteoblast lineage. Mol. Cell. Biol., 2011, 31, 4593-4608.
[35]
Cox, J.L.; Mallanna, S.K.; Luo, X.; Rizzino, A. Sox2 uses multiple domains to associate with proteins present in Sox2-protein complexes. PLoS One, 2010, 5, e15486.
[36]
Liu, Y.R.; Laghari, Z.A.; Novoa, C.A.; Hughes, J.; Webster, J.R.M.; Goodwin, P.E.; Wheatley, S.P.; Scotting, P.J. Sox2 acts as a transcriptional repressor in neural stem cells. BMC Neurosci., 2014, 15, 95.
[37]
Kamachi, Y.; Uchikawa, M.; Tanouchi, A.; Sekido, R.; Kondoh, H. Pax6 and SOX2 form a Co-DNA-binding partner complex that regulates initiation of lens development. Genes Dev., 2001, 15, 1272-1286.
[38]
Yuan, H.; Corbi, N.; Basilico, C.; Dailey, L. Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3. Genes Dev., 1995, 9, 2635-2645.
[39]
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126, 663-676.
[40]
Engelen, E.; Akinci, U.; Bryne, J.C.; Hou, J.; Gontan, C.; Moen, M.; Szumska, D.; Kockx, C.; Van Ijcken, W.; Dekkers, D.H.W.; Demmers, J.; Rijkers, E.J.; Bhattacharya, S.; Philipsen, S.; Pevny, L.H.; Grosveld, F.G.; Rottier, R.J.; Lenhard, B.; Poot, R.A. Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes. Nat. Genet., 2011, 43, 607-611.
[41]
Ahmed, M.; Wong, E.Y.M.; Sun, J.; Xu, J.; Wang, F.; Xu, P.X. Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating atoh1 expression in cooperation with Sox2. Dev. Cell, 2012, 22, 377-390.
[42]
Neves, J.; Uchikawa, M.; Bigas, A.; Giraldez, F. The prosensory function of Sox2 in the chicken inner ear relies on the direct regulation of Aoh1. PLoS One, 2012, 7, e30871.
[43]
Aksoy, I.; Jauch, R.; Chen, J.; Dyla, M.; Divakar, U.; Bogu, G.K.; Teo, R.; Leng Ng, C.K.; Herath, W.; Lili, S.; Hutchins, A.P.; Robson, P.; Kolatkar, P.R.; Stanton, L.W. Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. EMBO J., 2013, 32, 938-953.
[44]
Jauch, R.; Aksoy, I.; Hutchins, A.P.; Ng, C.K.L.; Tian, X.F.; Chen, J.; Palasingam, P.; Robson, P.; Stanton, L.W.; Kolatkar, P.R. Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA. Stem Cells, 2011, 29, 940-951.
[45]
Mallanna, S.K.; Ormsbee, B.D.; Iacovino, M.; Gilmore, J.M.; Cox, J.L.; Kyba, M.; Washburn, M.P.; Rizzino, A. Proteomic analysis of Sox2-associated proteins during early stages of mouse embryonic stem cell differentiation identifies Sox21 as a novel regulator of stem cell fate. Stem Cells, 2010, 28, 1715-1727.
[46]
Huttlin, E.L.; Ting, L.; Bruckner, R.J.; Gebreab, F.; Gygi, M.P.; Szpyt, J.; Tam, S.; Zarraga, G.; Colby, G.; Baltier, K.; Dong, R.; Guarani, V.; Vaites, L.P.; Ordureau, A.; Rad, R.; Erickson, B.K.; Wühr, M.; Chick, J.; Zhai, B.; Kolippakkam, D.; Mintseris, J.; Obar, R.A.; Harris, T.; Artavanis-Tsakonas, S.; Sowa, M.E.; De Camilli, P.; Paulo, J.A.; Harper, J.W.; Gygi, S.P. The BioPlex network: A systematic exploration of the human interactome. Cell, 2015, 162, 425-440.
[47]
Huttlin, E.L.; Bruckner, R.J.; Paulo, J.A.; Cannon, J.R.; Ting, L.; Baltier, K.; Colby, G.; Gebreab, F.; Gygi, M.P.; Parzen, H.; Szpyt, J.; Tam, S.; Zarraga, G.; Pontano-Vaites, L.; Swarup, S.; White, A.E.; Schweppe, D.K.; Rad, R.; Erickson, B.K.; Obar, R.A.; Guruharsha, K.G.; Li, K.; Artavanis-Tsakonas, S.; Gygi, S.P.; Wade Harper, J. Architecture of the human interactome defines protein communities and disease networks. Nature, 2017, 545, 505-509.
[48]
Shimozaki, K.; Zhang, C.L.; Suh, H.; Denli, A.M.; Evans, R.M.; Gage, F.H. SRY-Box-containing gene 2 regulation of nuclear receptor tailless (Tlx) transcription in adult neural stem cells. J. Biol. Chem., 2012, 287, 5969-5978.
[49]
Fong, Y.W.; Inouye, C.; Yamaguchi, T.; Cattoglio, C.; Grubisic, I.; Tjian, R. A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells. Cell, 2011, 147, 120-131.
[50]
Gao, Z.; Cox, J.L.; Gilmore, J.M.; Ormsbee, B.D.; Mallanna, S.K.; Washburn, M.P.; Rizzino, A. Determination of protein interactome of transcription factor Sox2 in embryonic stem cells engineered for inducible expression of four reprogramming factors. J. Biol. Chem., 2012, 287, 11384-11397.
[51]
Vescovi, A.L.; Galli, R.; Reynolds, B.A. Brain tumor stem cells. Nat. Rev. Cancer, 2006, 6, 425-436.
[52]
Singh, S.K.; Clarke, I.D.; Terasaki, M.; Bonn, V.E.; Hawkins, C.; Squire, J.; Dirks, P.B. Identification of a cancer stem cell in human brain tumors. Cancer Res., 2003, 63, 5821-5828.
[53]
Biddle, A.; Liang, X.; Gammon, L.; Fazil, B.; Harper, L.J.; Emich, H.; Costea, D.E.; Mackenzie, I.C. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res., 2011, 71, 5317-5326.
[54]
Da Silva-Diz, V.; Simon-Extremera, P.; Bernat-Peguera, A.; De Sostoa, J.; Urpí, M.; Penín, R.M.; Sidelnikova, D.P.; Bermejo, O.; Vinals, J.M.; Rodolosse, A.; Gonzalez-Suarez, E.; Moruno, A.G.; Pujana, M.A.; Esteller, M.; Villanueva, A.; Vinals, F.; Munoz, P. Cancer stem-like cells act via distinct signaling pathways in promoting late stages of malignant progression. Cancer Res., 2016, 76, 1245-1259.
[55]
Zhang, Q.; Shi, S.; Yen, Y.; Brown, J.; Ta, J.Q.; Le, A.D. A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett., 2010, 289, 151-160.
[56]
Favaro, R.; Appolloni, I.; Pellegatta, S.; Sanga, A.B.; Pagella, P.; Gambini, E.; Pisati, F.; Ottolenghi, S.; Foti, M.; Finocchiaro, G.; Malatesta, P.; Nicolis, S.K. Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma. Cancer Res., 2014, 74, 1833-1844.
[57]
Li, X.; Xu, Y.; Chen, Y.; Chen, S.; Jia, X.; Sun, T.; Liu, Y.; Li, X.; Xiang, R.; Li, N. SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/β-catenin signal network. Cancer Lett., 2013, 336, 379-389.
[58]
Liu, X.; Qiao, B.; Zhao, T.; Hu, F.; Lam, A.K.; Tao, Q. Sox2 promotes tumor aggressiveness and epithelial‑mesenchymal transition in tongue squamous cell carcinoma. Int. J. Mol. Med., 2018, 42, 1418-1426.
[59]
Cimadamore, F.; Amador-Arjona, A.; Chen, C.; Huang, C.T.; Terskikh, A.V. SOX2-LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors. Proc. Natl. Acad. Sci. USA, 2013, 110, E3017-E3026.
[60]
Tsuji, T.; Ibaragi, S.; Hu, G.F. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res., 2009, 69, 7135-7139.
[61]
Thiery, J.P.; Acloque, H.; Huang, R.Y.J.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139, 871-890.
[62]
Polyak, K.; Weinberg, R.A. Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nat. Rev. Cancer, 2009, 9, 265-273.
[63]
Zha, L.; Zhang, J.; Tang, W.; Zhang, N.; He, M.; Guo, Y.; Wang, Z. HMGA2 elicits EMT by activating the Wnt/β-catenin pathway in gastric cancer. Dig. Dis. Sci., 2013, 58, 724-733.
[64]
Wu, Y.; Ginther, C.; Kim, J.; Mosher, N.; Chung, S.; Slamon, D.; Vadgama, J.V. Expression of Wnt3 activates Wnt/ -catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells. Mol. Cancer Res., 2012, 10, 1597-1606.
[65]
Chen, Y.; Shi, L.; Zhang, L.; Li, R.; Liang, J.; Yu, W.; Sun, L.; Yang, X.; Wang, Y.; Zhang, Y.; Shang, Y. The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer. J. Biol. Chem., 2008, 283, 17969-17978.
[66]
Kregel, S.; Kiriluk, K.J.; Rosen, A.M.; Cai, Y.; Reyes, E.E.; Otto, K.B.; Tom, W.; Paner, G.P.; Szmulewitz, R.Z.; Vander Griend, D.J. Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer. PLoS One, 2013, 8, e53701.
[67]
Fang, X.; Yu, W.; Li, L.; Shao, J.; Zhao, N.; Chen, Q.; Ye, Z.; Lin, S.C.; Zheng, S.; Lin, B. ChIP-Seq and functional analysis of the SOX2 gene in colorectal cancers. Omi. A. J. Integr. Biol., 2010, 14, 369-384.
[68]
Singh, S.; Trevino, J.; Bora-Singhal, N.; Coppola, D.; Haura, E.; Altiok, S.; Chellappan, S.P. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer. Mol. Cancer, 2012, 11, 73.
[69]
Lin, F.; Lin, P.; Zhao, D.; Chen, Y.; Xiao, L.; Qin, W.; Li, D.; Chen, H.; Zhao, B.; Zou, H.; Zheng, X.; Yu, X. Sox2 targets cyclinE, p27 and survivin to regulate androgen-independent human prostate cancer cell proliferation and apoptosis. Cell Prolif., 2012, 45, 207-216.
[70]
Takanaga, H.; Tsuchida-Straeten, N.; Nishide, K.; Watanabe, A.; Aburatani, H.; Kondo, T. Gli2 is a novel regulator of Sox2 expression in telencephalic neuroepithelial cells. Stem Cells, 2009, 27, 165-174.
[71]
Gangemi, R.M.R.; Griffero, F.; Marubbi, D.; Perera, M.; Capra, M.C.; Malatesta, P.; Ravetti, G.L.; Zona, G.L.; Daga, A.; Corte, G. SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells, 2009, 27, 40-48.
[72]
Clement, V.; Sanchez, P.; de Tribolet, N.; Radovanovic, I.; Ruiz i Altaba, A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr. Biol., 2007, 17, 165-172.
[73]
Rousso, S.Z.; Schyr, R.B.H.; Gur, M.; Zouela, N.; Kot-Leibovich, H.; Shabtai, Y.; Koutsi-Urshanski, N.; Baldessari, D.; Pillemer, G.; Niehrs, C.; Fainsod, A. Negative autoregulation of Oct3/4 through Cdx1 promotes the onset of gastrulation. Dev. Dyn., 2011, 240, 796-807.
[74]
Béland, M.; Pilon, N.; Houle, M.; Oh, K.; Sylvestre, J-R.; Prinos, P.; Lohnes, D. Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex. Mol. Cell. Biol., 2004, 24, 5028-5038.
[75]
Fang, X.; Yoon, J.G.; Li, L.; Yu, W.; Shao, J.; Hua, D.; Zheng, S.; Hood, L.; Goodlett, D.R.; Foltz, G.; Lin, B. The SOX2 response program in glioblastoma multiforme: An integrated ChIP-Seq, expression microarray, and microRNA analysis. BMC Genomics, 2011, 12, 11.
[76]
Cox, J.L.; Wilder, P.J.; Gilmore, J.M.; Wuebben, E.L.; Washburn, M.P.; Rizzino, A. The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells. PLoS One, 2013, 8, e62857.
[77]
Alonso, M.M.; Diez-Valle, R.; Manterola, L.; Rubio, A.; Liu, D.; Cortes-Santiago, N.; Urquiza, L.; Jauregi, P.; de Munain, A.L.; Sampron, N.; Aramburu, A.; Tejada-Solís, S.; Vicente, C.; Odero, M.D.; Bandrés, E.; García-Foncillas, J.; Idoate, M.A.; Lang, F.F.; Fueyo, J.; Gomez-Manzano, C. Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas. PLoS One, 2011, 6, e26740.
[78]
Bass, A.J.; Watanabe, H.; Mermel, C.H.; Yu, S.; Perner, S.; Verhaak, R.G.; Kim, S.Y.; Wardwell, L.; Tamayo, P.; Gat-Viks, I.; Ramos, A.H.; Woo, M.S.; Weir, B.A.; Getz, G.; Beroukhim, R.; O’Kelly, M.; Dutt, A.; Rozenblatt-Rosen, O.; Dziunycz, P.; Komisarof, J.; Chirieac, L.R.; Lafargue, C.J.; Scheble, V.; Wilbertz, T.; Ma, C.; Rao, S.; Nakagawa, H.; Stairs, D.B.; Lin, L.; Giordano, T.J.; Wagner, P.; Minna, J.D.; Gazdar, A.F.; Zhu, C.Q.; Brose, M.S.; Cecconello, I.; Ribeiro, U.; Marie, S.K.; Dahl, O.; Shivdasani, R.A.; Tsao, M.S.; Rubin, M.A.; Wong, K.K.; Regev, A.; Hahn, W.C.; Beer, D.G.; Rustgi, A.K.; Meyerson, M. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat. Genet., 2009, 41, 1238-1242.
[79]
Xiang, R.; Liao, D.; Cheng, T.; Zhou, H.; Shi, Q.; Chuang, T.S.; Markowitz, D.; Reisfeld, R.A.; Luo, Y. Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer. Br. J. Cancer, 2011, 104, 1410-1417.
[80]
Chen, S.; Xu, Y.; Chen, Y.; Li, X.; Mou, W.; Wang, L.; Liu, Y.; Reisfeld, R.A.; Xiang, R.; Lv, D.; Li, N. SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells. PLoS One, 2012, 7, e36326.
[81]
Rudin, C.M.; Durinck, S.; Stawiski, E.W.; Poirier, J.T.; Modrusan, Z.; Shames, D.S.; Bergbower, E.A.; Guan, Y.; Shin, J.; Guillory, J.; Rivers, C.S.; Foo, C.K.; Bhatt, D.; Stinson, J.; Gnad, F.; Haverty, P.M.; Gentleman, R.; Chaudhuri, S.; Janakiraman, V.; Jaiswal, B.S.; Parikh, C.; Yuan, W.; Zhang, Z.; Koeppen, H.; Wu, T.D.; Stern, H.M.; Yauch, R.L.; Huffman, K.E.; Paskulin, D.D.; Illei, P.B.; Varella-Garcia, M.; Gazdar, A.F.; De Sauvage, F.J.; Bourgon, R.; Minna, J.D.; Brock, M.V.; Seshagiri, S. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat. Genet., 2012, 44, 1111-1116.
[82]
Yokota, E.; Yamatsuji, T.; Takaoka, M.; Haisa, M.; Takigawa, N.; Miyake, N.; Ikeda, T.; Mori, T.; Ohno, S.; Sera, T.; Fukazawa, T.; Naomoto, Y. Targeted silencing of SOX2 by an artificial transcription factor showed antitumor effect in lung and esophageal squamous cell carcinoma. Oncotarget, 2017, 8, 103063-103076.
[83]
Zheng, J.; Xu, L.; Pan, Y.; Yu, S.; Wang, H.; Kennedy, D.; Zhang, Y. Sox2 Modulates motility and enhances progression of colorectal cancer via the Rho-ROCK signaling pathway. Oncotarget, 2017, 8, 98635-98645.
[84]
Otsubo, T.; Akiyama, Y.; Hashimoto, Y.; Shimada, S.; Goto, K.; Yuasa, Y. MicroRNA-126 inhibits Sox2 expression and contributes to gastric carcinogenesis. PLoS One, 2011, 6, e16617.
[85]
Otsubo, T.; Akiyama, Y.; Yanagihara, K.; Yuasa, Y. SOX2 Is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis. Br. J. Cancer, 2008, 98, 824-831.
[86]
Uozaki, H.; Barua, R.R.; Minhua, S.; Ushiku, T.; Hino, R.; Shinozaki, A.; Sakatani, T.; Fukayama, M. Transcriptional factor typing with SOX2, HNF4aP1, and CDX2 closely relates to tumor invasion and epstein-barr virus status in gastric cancer. Int. J. Clin. Exp. Pathol., 2011, 4, 230-240.
[87]
Tsukamoto, T.; Inada, K.; Tanaka, H.; Mizoshita, T.; Mihara, M.; Ushijima, T.; Yamamura, Y.; Nakamura, S.; Tatematsu, M. Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: Inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia. J. Cancer Res. Clin. Oncol., 2004, 130, 135-145.
[88]
Neumann, J.; Bahr, F.; Horst, D.; Kriegl, L.; Engel, J.; Luque, R.M.; Gerhard, M.; Kirchner, T.; Jung, A. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer, 2011, 11, 518.
[89]
Jia, X.; Li, X.; Xu, Y.; Zhang, S.; Mou, W.; Liu, Y.; Liu, Y.; Lv, D.; Liu, C.H.; Tan, X.; Xiang, R.; Li, N. SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell. J. Mol. Cell Biol., 2011, 3, 230-238.
[90]
Oppel, F.; Müller, N.; Schackert, G.; Hendruschk, S.; Martin, D.; Geiger, K.D.; Temme, A. SOX2-RNAi attenuates S-phase entry and induces RhoA-dependent switch to protease-independent amoeboid migration in human glioma cells. Mol. Cancer, 2011, 10, 137.
[91]
Stolzenburg, S.; Rots, M.G.; Beltran, A.S.; Rivenbark, A.G.; Yuan, X.; Qian, H.; Strahl, B.D.; Blancafort, P. Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Res., 2012, 40, 6725-6740.
[92]
Lee, S.H.; Oh, S.Y.; Do, S.I.; Lee, H.J.; Kang, H.J.; Rho, Y.S.; Bae, W.J.; Lim, Y.C. SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma. Br. J. Cancer, 2014, 111, 2122-2130.
[93]
Yang, S.; Zheng, J.; Xiao, X.; Xu, T.; Tang, W.; Zhu, H.; Yang, L.; Zheng, S.; Dong, K.; Zhou, G.; Wang, Y. SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells. Int. J. Oncol., 2015, 46, 317-323.
[94]
Jiang, X.D.; Luo, G.; Wang, X.H.; Chen, L.L.; Ke, X.; Li, Y. Expression of Oct4 and Sox2 and their clinical significance in tongue squamous cell carcinoma. Zhonghua Kou Qiang Yi Xue Za Zhi, 2017, 52, 27-33.
[95]
Zhu, F.; Qian, W.; Zhang, H.; Liang, Y.; Wu, M.; Zhang, Y.; Zhang, X.; Gao, Q.; Li, Y. SOX2 is a marker for stem-like tumor cells in bladder cancer. Stem Cell Reports, 2017, 9, 429-437.
[96]
Li, Q.; Liu, F.; Zhang, Y.; Fu, L.; Wang, C.; Chen, X.; Guan, S.; Meng, X. Association of SOX2&NestinDNA amplification and protein expression with clinical features and overall survival in non-small cell lung cancer: A systematic review and meta-analysis. Oncotarget, 2016, 7, 34520-34531.
[97]
Oliviero, G.; Munawar, N.; Watson, A.; Streubel, G.; Manning, G.; Bardwell, V.; Bracken, A.P.; Cagney, G. The variant polycomb repressor complex 1 component PCGF1 interacts with a pluripotency sub-network that includes DPPA4, a regulator of embryogenesis. Sci. Rep., 2015, 5, 18388.
[98]
Xu, C.; Xie, D.; Yu, S.C.; Yang, X.J.; He, L.R.; Yang, J.; Ping, Y.F.; Wang, B.; Yang, L.; Xu, S.L.; Cui, W.; Wang, Q.L.; Fu, W.J.; Liu, Q.; Qian, C.; Cui, Y.H.; Rich, J.N.; Kung, H.F.; Zhang, X.; Bian, X.W. β-catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma. Cancer Res., 2013, 73, 3181-3189.
[99]
Foshay, K.M.; Gallicano, G.I. Regulation of Sox2 by STAT3 initiates commitment to the neural precursor cell fate. Stem Cells Dev., 2008, 17, 269-278.
[100]
Tanimura, N.; Saito, M.; Ebisuya, M.; Nishida, E.; Ishikawa, F. Stemness-related factor Sall4 interacts with transcription factors Oct-3/4 and Sox2 and occupies Oct-Sox elements in mouse embryonic stem cells. J. Biol. Chem., 2013, 288, 5027-5038.
[101]
Wei, Z.; Yang, Y.; Zhang, P.; Andrianakos, R.; Hasegawa, K.; Lyu, J.; Chen, X.; Bai, G.; Liu, C.; Pera, M.; Lu, W. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells, 2009, 27, 2969-2978.
[102]
Schmidt, R.; Plath, K. The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation. Genome Biol., 2012, 13, 251.
[103]
Aota, S.I.; Nakajima, N.; Sakamoto, R.; Watanabe, S.; Ibaraki, N.; Okazaki, K. Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene. Dev. Biol., 2003, 257, 1-13.
[104]
Ravasi, T.; Suzuki, H.; Cannistraci, C.V.; Katayama, S.; Bajic, V.B.; Tan, K.; Akalin, A.; Schmeier, S.; Kanamori-Katayama, M.; Bertin, N.; Carninci, P.; Daub, C.O.; Forrest, A.R.R.; Gough, J.; Grimmond, S.; Han, J.H.; Hashimoto, T.; Hide, W.; Hofmann, O.; Kawaji, H.; Kubosaki, A.; Lassmann, T.; van Nimwegen, E.; Ogawa, C.; Teasdale, R.D.; Tegnér, J.; Lenhard, B.; Teichmann, S.A.; Arakawa, T.; Ninomiya, N.; Murakami, K.; Tagami, M.; Fukuda, S.; Imamura, K.; Kai, C.; Ishihara, R.; Kitazume, Y.; Kawai, J.; Hume, D.A.; Ideker, T.; Hayashizaki, Y. An atlas of combinatorial transcriptional regulation in mouse and man. Cell, 2010, 140, 744-752.
[105]
Fukushima, H.; Ogura, K.; Wan, L.; Lu, Y.; Li, V.; Gao, D.; Liu, P.; Lau, A.W.; Wu, T.; Kirschner, M.W.; Inuzuka, H.; Wei, W. SCF-mediated cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Reports, 2013, 4, 803-816.
[106]
Trowe, M.O.; Zhao, L.; Weiss, A.C.; Christoffels, V.; Epstein, D.J.; Kispert, A. Inhibition of Sox2-dependent activation of shh in the ventral diencephalon by Tbx3 is required for formation of the neurohypophysis. Development, 2013, 140, 2299-2309.

Rights & Permissions Print Cite
Article Metrics
142
14
1
1
World Immunization Week
© 2024 Bentham Science Publishers | Privacy Policy