Journal of Mammary Gland Biology and Neoplasia

, Volume 24, Issue 3, pp 213–230 | Cite as

Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance

  • Gaurav A. Mehta
  • Pooja Khanna
  • Michael L. GatzaEmail author


The SOX genes encode a family of more than 20 transcription factors that are critical regulators of embryogenesis and developmental processes and, when aberrantly expressed, have been shown to contribute to tumor development and progression in both an oncogenic and tumor suppressive role. Increasing evidence demonstrates that the SOX proteins play essential roles in multiple cellular processes that mediate or contribute to oncogenic transformation and tumor progression. In the context of breast cancer, SOX proteins function both as oncogenes and tumor suppressors and have been shown to be associated with tumor stage and grade and poor prognosis. Experimental evidence demonstrates that a subset of SOX proteins regulate critical aspects of breast cancer biology including cancer stemness and multiple signaling pathways leading to altered cell proliferation, survival, and tumor development; EMT, cell migration and metastasis; as well as other tumor associated characteristics. This review will summarize the role of SOX family members as important mediators of tumorigenesis in breast cancer, with an emphasis on the triple negative or basal-like subtype of breast cancer, as well as examine the therapeutic potential of these genes and their downstream targets.


Sox Breast cancer Oncogene Cancer stem cells EMT Signaling 



While we have attempted to include all relevant studies in this manuscript, we apologize to those investigators whose work was not included due to spatial limitations. We would like to thank the members of our lab for critical reading of this manuscript. This work is funded by post-doctoral fellowship DHFS-17PCC-002 from the New Jersey Commission for Cancer Research to G.A.M. and from the National Cancer Institute of the National Institutes of Health (CA166228), the V Foundation for Cancer Research (V2016-013), and the New Jersey Health Foundation (PC-17-18) to M.L.G.


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.Google Scholar
  2. 2.
    Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.PubMedPubMedCentralGoogle Scholar
  3. 3.
    The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.Google Scholar
  4. 4.
    Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012;486(7403):346–52.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell. 2015;163(2):506–19.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.PubMedGoogle Scholar
  7. 7.
    Gatza ML, Lucas JE, Barry WT, Kim JW, Wang Q, Crawford MD, et al. A pathway-based classification of human breast cancer. Proc Natl Acad Sci U S A. 2010;107(15):6994–9.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12(5):R68.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, et al. Proteogenomics connects somatic mutations to signalling in breast cancer. Nature. 2016;534(7605):55–62.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100(14):8418–23.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006;355(6):560–9.PubMedGoogle Scholar
  13. 13.
    Gatza ML, Silva GO, Parker JS, Fan C, Perou CM. An integrated genomics approach identifies drivers of proliferation in luminal-subtype human breast cancer. Nat Genet. 2014;46(10):1051–9.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Prat A, Fan C, Fernandez A, Hoadley KA, Martinello R, Vidal M, et al. Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. BMC Med. 2015;13:303.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, et al. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell. 2014;158(4):929–44.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Gross K, Wronski A, Skibinski A, Phillips S, Kuperwasser C. Cell fate decisions during breast cancer development. J Dev Biol. 2016;4(1):4.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Zhang M, Lee AV, Rosen JM. The cellular origin and evolution of breast cancer. Cold Spring Harb Perspect Med. 2017 Mar 1;7(3):a027128.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kamachi Y, Kondoh H. Sox proteins: regulators of cell fate specification and differentiation. Development. 2013;140(20):4129–44.PubMedGoogle Scholar
  19. 19.
    Sarkar A, Hochedlinger K. The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell. 2013;12(1):15–30.PubMedPubMedCentralGoogle Scholar
  20. 20.
    She ZY, Yang WX. SOX family transcription factors involved in diverse cellular events during development. Eur J Cell Biol. 2015;94(12):547–63.PubMedGoogle Scholar
  21. 21.
    Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, et al. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990;346(6281):245–50.PubMedGoogle Scholar
  22. 22.
    Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990;346(6281):240–4.PubMedGoogle Scholar
  23. 23.
    Tozbikian GH, Zynger DL. A combination of GATA3 and SOX10 is useful for the diagnosis of metastatic triple negative breast cancer. Hum Pathol. 2019;85:221-227.PubMedGoogle Scholar
  24. 24.
    Al-Zahrani KN, Cook DP, Vanderhyden BC, Sabourin LA. Assessing the efficacy of androgen receptor and Sox10 as independent markers of the triple-negative breast cancer subtype by transcriptome profiling. Oncotarget. 2018;9(70):33348–59.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Zang H, Li N, Pan Y, Hao J. Identification of upstream transcription factors (TFs) for expression signature genes in breast cancer. Gynecol Endocrinol. 2017;33(3):193–8.PubMedGoogle Scholar
  26. 26.
    Overman J, Fontaine F, Moustaqil M, Mittal D, Sierecki E, Sacilotto N, et al. Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice. Elife. 2017;6:e21221. Google Scholar
  27. 27.
    Nelson ER, Sharma R, Argani P, Cimino-Mathews A. Utility of Sox10 labeling in metastatic breast carcinomas. Hum Pathol. 2017;67:205–10.PubMedGoogle Scholar
  28. 28.
    Min L, Zhang C, Qu L, Huang J, Jiang L, Liu J, et al. Gene regulatory pattern analysis reveals essential role of core transcriptional factors’ activation in triple-negative breast cancer. Oncotarget. 2017;8(13):21938–53.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Feng X, Lu M. Expression of sex-determining region Y-box protein 2 in breast cancer and its clinical significance. Saudi Med J. 2017;38(7):685–90.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Feng W, Liu S, Zhu R, Li B, Zhu Z, Yang J, et al. SOX10 induced Nestin expression regulates cancer stem cell properties of TNBC cells. Biochem Biophys Res Commun. 2017;485(2):522–8.PubMedGoogle Scholar
  31. 31.
    Song L, Liu D, He J, Wang X, Dai Z, Zhao Y, et al. SOX1 inhibits breast cancer cell growth and invasion through suppressing the Wnt/beta-catenin signaling pathway. APMIS. 2016;124(7):547–55.PubMedGoogle Scholar
  32. 32.
    Shepherd JH, Uray IP, Mazumdar A, Tsimelzon A, Savage M, Hilsenbeck SG, et al. The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression. Oncotarget. 2016;7(11):13106–21.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Lei B, Zhang YX, Liu T, Li YW, Pang D. Sox9 upregulation in breast cancer is correlated with poor prognosis and the CD44(+)/CD24(-/low) phenotype. Int J Clin Exp Pathol. 2016;9(7):7345–51.Google Scholar
  34. 34.
    Ding H, Quan H, Yan W, Han J. Silencing of SOX12 by shRNA suppresses migration, invasion and proliferation of breast cancer cells. Biosci Rep. 2016;36(5):e00389.PubMedCentralGoogle Scholar
  35. 35.
    Ye X, Tam WL, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E, et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 2015;525(7568):256–60.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Pomp V, Leo C, Mauracher A, Korol D, Guo W, Varga Z. Differential expression of epithelial-mesenchymal transition and stem cell markers in intrinsic subtypes of breast cancer. Breast Cancer Res Treat. 2015;154(1):45–55.PubMedGoogle Scholar
  37. 37.
    Miettinen M, McCue PA, Sarlomo-Rikala M, Biernat W, Czapiewski P, Kopczynski J, et al. Sox10--a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol. 2015;39(6):826–35.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Fu D, Ren C, Tan H, Wei J, Zhu Y, He C, et al. Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer. Medicine (Baltimore). 2015;94(11):e637.Google Scholar
  39. 39.
    Pei XH, Lv XQ, Li HX. Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1. Biochem Biophys Res Commun. 2014;446(1):322–7.PubMedGoogle Scholar
  40. 40.
    Stovall DB, Wan M, Miller LD, Cao P, Maglic D, Zhang Q, et al. The regulation of SOX7 and its tumor suppressive role in breast cancer. Am J Pathol. 2013;183(5):1645–53.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Pula B, Olbromski M, Wojnar A, Gomulkiewicz A, Witkiewicz W, Ugorski M, et al. Impact of SOX18 expression in cancer cells and vessels on the outcome of invasive ductal breast carcinoma. Cell Oncol (Dordr). 2013;36(6):469–83.Google Scholar
  42. 42.
    Mohamed A, Gonzalez RS, Lawson D, Wang J, Cohen C. SOX10 expression in malignant melanoma, carcinoma, and normal tissues. Appl Immunohistochem Mol Morphol. 2013;21(6):506–10.PubMedGoogle Scholar
  43. 43.
    Ivanov SV, Panaccione A, Nonaka D, Prasad ML, Boyd KL, Brown B, et al. Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas. Br J Cancer. 2013;109(2):444–51.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Cimino-Mathews A, Subhawong AP, Elwood H, Warzecha HN, Sharma R, Park BH, et al. Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas. Hum Pathol. 2013;44(6):959–65.PubMedGoogle Scholar
  45. 45.
    Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 2012;31(11):1354–65.PubMedGoogle Scholar
  46. 46.
    Fu DY, Wang ZM, Li C, Wang BL, Shen ZZ, Huang W, 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.PubMedGoogle Scholar
  47. 47.
    Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, Rodriguez-Gil Y, Martinez MA, Hernandez L, et al. Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol. 2007;20(4):474–81.PubMedGoogle Scholar
  48. 48.
    Hunt SM, Clarke CL. Expression and hormonal regulation of the Sox4 gene in mouse female reproductive tissues. Biol Reprod. 1999;61(2):476–81.PubMedGoogle Scholar
  49. 49.
    Schilham MW, Oosterwegel MA, Moerer P, Ya J, de Boer PA, van de Wetering M, et al. Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4. Nature. 1996;380(6576):711–4.PubMedGoogle Scholar
  50. 50.
    Lefebvre V, Dumitriu B, Penzo-Mendez A, Han Y, Pallavi B. Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int J Biochem Cell Biol. 2007;39(12):2195–214.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Prior HM, Walter MA. SOX genes: architects of development. Mol Med. 1996;2(4):405–12.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Chew LJ, Gallo V. The Yin and Yang of Sox proteins: activation and repression in development and disease. J Neurosci Res. 2009;87(15):3277–87.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Thu KL, Becker-Santos DD, Radulovich N, Pikor LA, Lam WL, Tsao MS. SOX15 and other SOX family members are important mediators of tumorigenesis in multiple cancer types. Oncoscience. 2014;1(5):326–35.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Mehta GA, Parker JS, Silva GO, Hoadley KA, Perou CM, Gatza ML. Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer. Breast Cancer Res Treat. 2017;162(3):439–50.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Song GD, Sun Y, Shen H, Li W. SOX4 overexpression is a novel biomarker of malignant status and poor prognosis in breast cancer patients. Tumour Biol. 2015;36(6):4167–73.PubMedGoogle Scholar
  56. 56.
    Castillo SD, Matheu A, Mariani N, Carretero J, Lopez-Rios F, Lovell-Badge R, et al. Novel transcriptional targets of the SRY-HMG box transcription factor SOX4 link its expression to the development of small cell lung cancer. Cancer Res. 2012;72(1):176–86.PubMedGoogle Scholar
  57. 57.
    Liao YL, Sun YM, Chau GY, Chau YP, Lai TC, Wang JL, et al. Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma. Oncogene. 2008;27(42):5578–89.PubMedGoogle Scholar
  58. 58.
    Liu P, Ramachandran S, Ali Seyed M, Scharer CD, Laycock N, Dalton WB, et al. Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells. Cancer Res. 2006;66(8):4011–9.PubMedGoogle Scholar
  59. 59.
    Aaboe M, Birkenkamp-Demtroder K, Wiuf C, Sorensen FB, Thykjaer T, Sauter G, et al. SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization. Cancer Res. 2006;66(7):3434–42.PubMedGoogle Scholar
  60. 60.
    Lee CJ, Appleby VJ, Orme AT, Chan WI, Scotting PJ. Differential expression of SOX4 and SOX11 in medulloblastoma. J Neuro-Oncol. 2002;57(3):201–14.Google Scholar
  61. 61.
    Vervoort SJ, de Jong OG, Roukens MG, Frederiks CL, Vermeulen JF, Lourenco AR, et al. Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis. Elife. 2018;7:e27706.Google Scholar
  62. 62.
    Zhang J, Liang Q, Lei Y, Yao M, Li L, Gao X, et al. SOX4 induces epithelial-mesenchymal transition and contributes to breast cancer progression. Cancer Res. 2012;72(17):4597–608.PubMedGoogle Scholar
  63. 63.
    Dong P, Yu B, Pan L, Tian X, Liu F. Identification of Key genes and pathways in triple-negative breast cancer by integrated bioinformatics analysis. Biomed Res Int. 2018;2018:2760918.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Kundig P, Giesen C, Jackson H, Bodenmiller B, Papassotirolopus B, Freiberger SN, et al. Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer. J Transl Med. 2018;16(1):118.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Chakravarty G, Moroz K, Makridakis NM, Lloyd SA, Galvez SE, Canavello PR, et al. Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer. Exp Biol Med (Maywood). 2011;236(2):145–55.Google Scholar
  66. 66.
    Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Muller F, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 2011;11:42.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Liu P, Tang H, Song C, Wang J, Chen B, Huang X, et al. SOX2 promotes cell proliferation and metastasis in triple negative breast cancer. Front Pharmacol. 2018;9:942.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Mohammadi Yeganeh S, Vasei M, Tavakoli R, Kia V, Paryan M. The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells. Eur J Cancer Care (Engl). 2017;26(6):10.1111/ecc.12496. Google Scholar
  69. 69.
    Shen F, Cai WS, Feng Z, Li JL, Chen JW, Cao J, et al. MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression. Tumour Biol. 2015;36(3):1913–21.PubMedGoogle Scholar
  70. 70.
    Stovall DB, Cao P, Sui G. SOX7: from a developmental regulator to an emerging tumor suppressor. Histol Histopathol. 2014;29(4):439–45.PubMedGoogle Scholar
  71. 71.
    Yang F, Xiao Z, Zhang S. Knockdown of miR-194-5p inhibits cell proliferation, migration and invasion in breast cancer by regulating the Wnt/beta-catenin signaling pathway. Int J Mol Med. 2018;42(6):3355–63.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Liu H, Mastriani E, Yan ZQ, Yin SY, Zeng Z, Wang H, et al. SOX7 co-regulates Wnt/beta-catenin signaling with Axin-2: both expressed at low levels in breast cancer. Sci Rep. 2016;6:26136.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Katoh M. Expression of human SOX7 in normal tissues and tumors. Int J Mol Med. 2002;9(4):363–8.PubMedGoogle Scholar
  74. 74.
    Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med. 2007;58:267–84.PubMedGoogle Scholar
  75. 75.
    Spike BT, Engle DD, Lin JC, Cheung SK, La J, Wahl GM. A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. Cell Stem Cell. 2012;10(2):183–97.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Zvelebil M, Oliemuller E, Gao Q, Wansbury O, Mackay A, Kendrick H, et al. Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers. Breast Cancer Res. 2013;15(2):R25.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Adorno-Cruz V, Kibria G, Liu X, Doherty M, Junk DJ, Guan D, et al. Cancer stem cells: targeting the roots of cancer, seeds of metastasis, and sources of therapy resistance. Cancer Res. 2015;75(6):924–9.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Aiello NM, Stanger BZ. Echoes of the embryo: using the developmental biology toolkit to study cancer. Dis Model Mech. 2016;9(2):105–14.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Zhao D, Pan C, Sun J, Gilbert C, Drews-Elger K, Azzam DJ, et al. VEGF drives cancer-initiating stem cells through VEGFR-2/Stat3 signaling to upregulate Myc and Sox2. Oncogene. 2015;34(24):3107–19.PubMedGoogle Scholar
  80. 80.
    Visvader JE, Lindeman GJ. Cancer stem cells: current status and evolving complexities. Cell Stem Cell. 2012;10(6):717–28.PubMedGoogle Scholar
  81. 81.
    Wahl GM, Spike BT. Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity. NPJ Breast Cancer. 2017;3:14.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Piva M, Domenici G, Iriondo O, Rabano M, Simoes BM, Comaills V, et al. Sox2 promotes tamoxifen resistance in breast cancer cells. EMBO Mol Med. 2014;6(1):66–79.PubMedGoogle Scholar
  83. 83.
    Abdelalim EM, Emara MM, Kolatkar PR. The SOX transcription factors as key players in pluripotent stem cells. Stem Cells Dev. 2014;23(22):2687–99.PubMedGoogle Scholar
  84. 84.
    Grosschedl R, Giese K, Pagel J. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet. 1994;10(3):94–100.PubMedGoogle Scholar
  85. 85.
    Liu K, Lin B, Zhao M, Yang X, Chen M, Gao A, et al. The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cell Signal. 2013;25(5):1264–71.PubMedGoogle Scholar
  86. 86.
    Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140(1):62–73.PubMedGoogle Scholar
  87. 87.
    Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, et al. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 2012;148(5):1015–28.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Dravis C, Chung CY, Lytle NK, Herrera-Valdez J, Luna G, Trejo CL, et al. Epigenetic and transcriptomic profiling of mammary gland development and tumor models disclose regulators of cell state plasticity. Cancer Cell. 2018;34(3):466–82 e6.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Dravis C, Spike BT, Harrell JC, Johns C, Trejo CL, Southard-Smith EM, et al. Sox10 regulates stem/progenitor and mesenchymal cell states in mammary epithelial cells. Cell Rep. 2015;12(12):2035–48.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Oliemuller E, Kogata N, Bland P, Kriplani D, Daley F, Haider S, et al. SOX11 promotes invasive growth and ductal carcinoma in situ progression. J Pathol. 2017;243(2):193–207.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Stevanovic M, Zuffardi O, Collignon J, Lovell-Badge R, Goodfellow P. The cDNA sequence and chromosomal location of the human SOX2 gene. Mamm Genome. 1994;5(10):640–2.PubMedGoogle Scholar
  92. 92.
    Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003;17(1):126–40.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, et al. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 2007;9(6):625–35.PubMedGoogle Scholar
  94. 94.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.PubMedGoogle Scholar
  95. 95.
    Dong C, Wilhelm D, Koopman P. Sox genes and cancer. Cytogenet Genome Res. 2004;105(2-4):442–7.PubMedGoogle Scholar
  96. 96.
    Weina K, Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med. 2014;3:19.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Wuebben EL, Rizzino A. The dark side of SOX2: cancer - a comprehensive overview. Oncotarget. 2017;8(27):44917–43.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Gong X, Liu W, Wu L, Ma Z, Wang Y, Yu S, et al. Transcriptional repressor GATA binding 1-mediated repression of SRY-box 2 expression suppresses cancer stem cell functions and tumor initiation. J Biol Chem. 2018;293(48):18646–54.PubMedGoogle Scholar
  99. 99.
    Deng Z, Du WW, Fang L, Shan SW, Qian J, Lin J, et al. The intermediate filament vimentin mediates microRNA miR-378 function in cellular self-renewal by regulating the expression of the Sox2 transcription factor. J Biol Chem. 2013;288(1):319–31.PubMedGoogle Scholar
  100. 100.
    Zhang Y, Eades G, Yao Y, Li Q, Zhou Q. Estrogen receptor alpha signaling regulates breast tumor-initiating cells by down-regulating miR-140 which targets the transcription factor SOX2. J Biol Chem. 2012;287(49):41514–22.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Picon-Ruiz M, Pan C, Drews-Elger K, Jang K, Besser AH, Zhao D, et al. Interactions between adipocytes and breast cancer cells stimulate cytokine production and drive Src/Sox2/miR-302b-mediated malignant progression. Cancer Res. 2016;76(2):491–504.PubMedGoogle Scholar
  102. 102.
    Chen L, Xiao Z, Meng Y, Zhao Y, Han J, Su G, et al. The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. Biomaterials. 2012;33(5):1437–44.PubMedGoogle Scholar
  103. 103.
    Feng S, Duan X, Lo PK, Liu S, Liu X, Chen H, et al. Expansion of breast cancer stem cells with fibrous scaffolds. Integr Biol (Camb). 2013;5(5):768–77.Google Scholar
  104. 104.
    Bhola NE, Balko JM, Dugger TC, Kuba MG, Sanchez V, Sanders M, et al. TGF-beta inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Invest. 2013;123(3):1348–58.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Ikushima H, Todo T, Ino Y, Takahashi M, Saito N, Miyazawa K, et al. Glioma-initiating cells retain their tumorigenicity through integration of the Sox axis and Oct4 protein. J Biol Chem. 2011;286(48):41434–41.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Cheung M, Briscoe J. Neural crest development is regulated by the transcription factor Sox9. Development. 2003;130(23):5681–93.PubMedGoogle Scholar
  107. 107.
    Nowak JA, Polak L, Pasolli HA, Fuchs E. Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell. 2008;3(1):33–43.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Domenici G, Aurrekoetxea-Rodriguez I, Simoes BM, Rabano M, Lee SY, Millan JS, et al. A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells. 2019; Oncogene 38:3151–3169.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Wang C, Christin JR, Oktay MH, Guo W. Lineage-biased stem cells maintain estrogen-receptor-positive and -negative mouse mammary luminal lineages. Cell Rep. 2017;18(12):2825–35.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Xue Y, Lai L, Lian W, Tu X, Zhou J, Dong P, et al. SOX9/FXYD3/Src axis is critical for ER(+) breast cancer stem cell function. Mol Cancer Res. 2019;17(1):238-249.PubMedGoogle Scholar
  111. 111.
    Jeselsohn R, Cornwell M, Pun M, Buchwalter G, Nguyen M, Bango C, et al. Embryonic transcription factor SOX9 drives breast cancer endocrine resistance. Proc Natl Acad Sci U S A. 2017;114(22):E4482–E91.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, et al. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition. Oncogene. 2017;36(19):2737–49.PubMedGoogle Scholar
  113. 113.
    Li Q, Yao Y, Eades G, Liu Z, Zhang Y, Zhou Q. Downregulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer. Oncogene. 2014;33(20):2589–600.PubMedGoogle Scholar
  114. 114.
    Giraddi RR, Chung CY, Heinz RE, Balcioglu O, Novotny M, Trejo CL, et al. Single-cell transcriptomes distinguish stem cell state changes and lineage specification programs in early mammary gland development. Cell Rep. 2018;24(6):1653–66 e7.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Panaccione A, Guo Y, Yarbrough WG, Ivanov SV. Expression profiling of clinical specimens supports the existence of neural progenitor-like stem cells in basal breast cancers. Clin Breast Cancer. 2017;17(4):298–306 e7.PubMedPubMedCentralGoogle Scholar
  116. 116.
    Harbhajanka A, Chahar S, Miskimen K, Silverman P, Harris L, Williams N, et al. Clinicopathological, immunohistochemical and molecular correlation of neural crest transcription factor SOX10 expression in triple-negative breast carcinoma. Hum Pathol. 2018;80:163–9.PubMedGoogle Scholar
  117. 117.
    Laurent E, Begueret H, Bonhomme B, Veillon R, Thumerel M, Velasco V, et al. SOX10, GATA3, GCDFP15, androgen receptor, and mammaglobin for the differential diagnosis between triple-negative breast cancer and TTF1-negative lung adenocarcinoma. Am J Surg Pathol. 2019;43(3):293-302.PubMedGoogle Scholar
  118. 118.
    Bilir B, Osunkoya AO, Wiles WG, Sannigrahi S, Lefebvre V, Metzger D, et al. SOX4 is essential for prostate tumorigenesis initiated by PTEN Ablation. Cancer Res. 2016;76(5):1112–21.PubMedGoogle Scholar
  119. 119.
    Bilir B, Kucuk O, Moreno CS. Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells. J Transl Med. 2013;11:280.PubMedPubMedCentralGoogle Scholar
  120. 120.
    Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, et al. Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. Cancer Cell. 2013;23(6):768–83.Google Scholar
  121. 121.
    Vervoort SJ, Lourenco AR, Tufegdzic Vidakovic A, Mocholi E, Sandoval JL, Rueda OM, et al. SOX4 can redirect TGF-beta-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis. Nucleic Acids Res. 2018;46(18):9578–90.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Lee AK, Ahn SG, Yoon JH, Kim SA. Sox4 stimulates ss-catenin activity through induction of CK2. Oncol Rep. 2011;25(2):559–65.PubMedGoogle Scholar
  123. 123.
    Lopez-Knowles E, O'Toole SA, McNeil CM, Millar EK, Qiu MR, Crea P, et al. PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality. Int J Cancer. 2010;126(5):1121–31.PubMedGoogle Scholar
  124. 124.
    Zhang Y, Kwok-Shing Ng P, Kucherlapati M, Chen F, Liu Y, Tsang YH, et al. A pan-cancer proteogenomic atlas of PI3K/AKT/mTOR pathway alterations. Cancer Cell. 2017;31(6):820–32.e3.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13(2):140–56.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Hallstrom TC, Mori S, Nevins JR. An E2F1-dependent gene expression program that determines the balance between proliferation and cell death. Cancer Cell. 2008;13:11–22.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol. 2013;10(3):143–53.PubMedGoogle Scholar
  128. 128.
    Wong KK, Engelman JA, Cantley LC. Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev. 2010;20(1):87–90.PubMedGoogle Scholar
  129. 129.
    Ramezani-Rad P, Geng H, Hurtz C, Chan LN, Chen Z, Jumaa H, et al. SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia. Blood. 2013;121(1):148–55.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4(5):a008052. PubMedPubMedCentralGoogle Scholar
  131. 131.
    Khramtsov AI, Khramtsova GF, Tretiakova M, Huo D, Olopade OI, Goss KH. Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am J Pathol. 2010;176(6):2911–20.PubMedPubMedCentralGoogle Scholar
  132. 132.
    Chen Y, Shi L, Zhang L, Li R, Liang J, Yu W, et al. The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer. J Biol Chem. 2008;283(26):17969–78.PubMedGoogle Scholar
  133. 133.
    Ye X, Wu F, Wu C, Wang P, Jung K, Gopal K, et al. beta-Catenin, a Sox2 binding partner, regulates the DNA binding and transcriptional activity of Sox2 in breast cancer cells. Cell Signal. 2014;26(3):492–501.PubMedGoogle Scholar
  134. 134.
    Liu K, Xie F, Gao A, Zhang R, Zhang L, Xiao Z, et al. SOX2 regulates multiple malignant processes of breast cancer development through the SOX2/miR-181a-5p, miR-30e-5p/TUSC3 axis. Mol Cancer. 2017;16(1):62.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Wang J, Zeng H, Li H, Chen T, Wang L, Zhang K, et al. MicroRNA-101 inhibits growth, proliferation and migration and induces apoptosis of breast cancer cells by targeting sex-determining region Y-Box 2. Cell Physiol Biochem. 2017;43(2):717–32.PubMedGoogle Scholar
  136. 136.
    Zhu YT, Jia Y, Hu L, Qi C, Prasad MK, McCallion AS, et al. Peroxisome-proliferator-activated receptor-binding protein (PBP) is essential for the growth of active Notch4-immortalized mammary epithelial cells by activating SOX10 expression. Biochem J. 2009;425(2):435–44.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Cao Q, Chen X, Wu X, Liao R, Huang P, Tan Y, et al. Inhibition of UGT8 suppresses basal-like breast cancer progression by attenuating sulfatide-alphaVbeta5 axis. J Exp Med. 2018;215(6):1679–92.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Wang QY, Zhou CX, Zhan MN, Tang J, Wang CL, Ma CN, et al. MiR-133b targets Sox9 to control pathogenesis and metastasis of breast cancer. Cell Death Dis. 2018;9(7):752.PubMedPubMedCentralGoogle Scholar
  139. 139.
    Zhao Y, Pang W, Yang N, Hao L, Wang L. MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway. Int J Oncol. 2018;53(6):2715–26.PubMedGoogle Scholar
  140. 140.
    Chen X, Fu Y, Xu H, Teng P, Xie Q, Zhang Y, et al. SOX5 predicts poor prognosis in lung adenocarcinoma and promotes tumor metastasis through epithelial-mesenchymal transition. Oncotarget. 2018;9(13):10891–904.PubMedGoogle Scholar
  141. 141.
    Zhang D, Liu S. SOX5 promotes epithelial-mesenchymal transition in osteosarcoma via regulation of Snail. J BUON. 2017;22(1):258–64.PubMedGoogle Scholar
  142. 142.
    Si C, Yu Q, Yao Y. Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5. Exp Ther Med. 2018;15(5):4515–21.PubMedPubMedCentralGoogle Scholar
  143. 143.
    Young N, Hahn CN, Poh A, Dong C, Wilhelm D, Olsson J, et al. Effect of disrupted SOX18 transcription factor function on tumor growth, vascularization, and endothelial development. J Natl Cancer Inst. 2006;98(15):1060–7.PubMedGoogle Scholar
  144. 144.
    Zhang J, Ma Y, Wang S, Chen F, Gu Y. Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells. Oncol Rep. 2016;35(6):3721–7.PubMedGoogle Scholar
  145. 145.
    Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8.PubMedPubMedCentralGoogle Scholar
  146. 146.
    Li X, Xu Y, Chen Y, Chen S, Jia X, Sun T, et al. SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/beta-catenin signal network. Cancer Lett. 2013;336(2):379–89.PubMedGoogle Scholar
  147. 147.
    Pang Y, Liu J, Li X, Xiao G, Wang H, Yang G, et al. MYC and DNMT3A-mediated DNA methylation represses microRNA-200b in triple negative breast cancer. J Cell Mol Med. 2018;22(12):6262–74.PubMedPubMedCentralGoogle Scholar
  148. 148.
    Vervoort SJ, Lourenco AR, van Boxtel R, Coffer PJ. SOX4 mediates TGF-beta-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition. PLoS One. 2013;8(1):e53238.PubMedPubMedCentralGoogle Scholar
  149. 149.
    Heldin CH, Vanlandewijck M, Moustakas A. Regulation of EMT by TGFbeta in cancer. FEBS Lett. 2012;586(14):1959–70.PubMedGoogle Scholar
  150. 150.
    Jafarnejad SM, Wani AA, Martinka M, Li G. Prognostic significance of Sox4 expression in human cutaneous melanoma and its role in cell migration and invasion. Am J Pathol. 2010;177(6):2741–52.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–52.PubMedPubMedCentralGoogle Scholar
  152. 152.
    Xi J, Feng J, Zeng S. Long noncoding RNA lncBRM facilitates the proliferation, migration and invasion of ovarian cancer cells via upregulation of Sox4. Am J Cancer Res. 2017;7(11):2180–9.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Yang M, Wang J, Wang L, Shen C, Su B, Qi M, et al. Estrogen induces androgen-repressed SOX4 expression to promote progression of prostate cancer cells. Prostate. 2015;75(13):1363–75.PubMedGoogle Scholar
  154. 154.
    Zhou Y, Wang X, Huang Y, Chen Y, Zhao G, Yao Q, et al. Down-regulated SOX4 expression suppresses cell proliferation, metastasis and induces apoptosis in Xuanwei female lung cancer patients. J Cell Biochem. 2015;116(6):1007–18.PubMedGoogle Scholar
  155. 155.
    Lee H, Goodarzi H, Tavazoie SF, Alarcon CR. TMEM2 is a SOX4-regulated gene that mediates metastatic migration and invasion in breast cancer. Cancer Res. 2016;76(17):4994–5005.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Liu S, Patel SH, Ginestier C, Ibarra I, Martin-Trevino R, Bai S, et al. MicroRNA93 regulates proliferation and differentiation of normal and malignant breast stem cells. PLoS Genet. 2012;8(6):e1002751.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Bai JW, Wang X, Zhang YF, Yao GD, Liu H. MicroRNA-320 inhibits cell proliferation and invasion in breast cancer cells by targeting SOX4. Oncol Lett. 2017;14(6):7145–52.PubMedPubMedCentralGoogle Scholar
  158. 158.
    Hanieh H. Aryl hydrocarbon receptor-microRNA-212/132 axis in human breast cancer suppresses metastasis by targeting SOX4. Mol Cancer. 2015;14:172.PubMedPubMedCentralGoogle Scholar
  159. 159.
    Jin Y, Zhao M, Xie Q, Zhang H, Wang Q, Ma Q. MicroRNA-338-3p functions as tumor suppressor in breast cancer by targeting SOX4. Int J Oncol. 2015;47(4):1594–602.PubMedGoogle Scholar
  160. 160.
    Wang N, Liu W, Zheng Y, Wang S, Yang B, Li M, et al. CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-kappaB/SOX4 signaling. Cell Death Dis. 2018;9(9):880.PubMedPubMedCentralGoogle Scholar
  161. 161.
    Yang F, Shen Y, Zhang W, Jin J, Huang D, Fang H, et al. An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer. Cell Death Differ. 2018;25(12):2209-220.Google Scholar
  162. 162.
    Hu J, Tian J, Zhu S, Sun L, Yu J, Tian H, et al. Sox5 contributes to prostate cancer metastasis and is a master regulator of TGF-beta-induced epithelial mesenchymal transition through controlling Twist1 expression. Br J Cancer. 2018;118(1):88–97.PubMedGoogle Scholar
  163. 163.
    Renjie W, Haiqian L. MiR-132, miR-15a and miR-16 synergistically inhibit pituitary tumor cell proliferation, invasion and migration by targeting Sox5. Cancer Lett. 2015;356(2 Pt B):568–78.PubMedGoogle Scholar
  164. 164.
    Wang D, Han S, Wang X, Peng R, Li X. SOX5 promotes epithelial-mesenchymal transition and cell invasion via regulation of Twist1 in hepatocellular carcinoma. Med Oncol. 2015;32(2):461.PubMedGoogle Scholar
  165. 165.
    Yang B, Zhang W, Sun D, Wei X, Ding Y, Ma Y, et al. Downregulation of miR-139-5p promotes prostate cancer progression through regulation of SOX5. Biomed Pharmacother. 2019;109:2128–35.PubMedGoogle Scholar
  166. 166.
    Zhang YJ, Xu F, Zhang YJ, Li HB, Han JC, Li L. miR-206 inhibits non small cell lung cancer cell proliferation and invasion by targeting SOX9. Int J Clin Exp Med. 2015;8(6):9107–13.PubMedPubMedCentralGoogle Scholar
  167. 167.
    Narasimhan K, Pillay S, Bin Ahmad NR, Bikadi Z, Hazai E, Yan L, et al. Identification of a polyoxometalate inhibitor of the DNA binding activity of Sox2. ACS Chem Biol. 2011;6(6):573–81.PubMedGoogle Scholar
  168. 168.
    Chen X, Zheng Q, Li W, Lu Y, Ni Y, Ma L, et al. SOX5 induces lung adenocarcinoma angiogenesis by inducing the expression of VEGF through STAT3 signaling. Onco Targets Ther. 2018;11:5733–41.PubMedPubMedCentralGoogle Scholar
  169. 169.
    Yang H, Lee S, Lee S, Kim K, Yang Y, Kim JH, et al. Sox17 promotes tumor angiogenesis and destabilizes tumor vessels in mice. J Clin Invest. 2013;123(1):418–31.PubMedGoogle Scholar
  170. 170.
    Bojang P Jr, Ramos KS. The promise and failures of epigenetic therapies for cancer treatment. Cancer Treat Rev. 2014;40(1):153–69.PubMedGoogle Scholar
  171. 171.
    Mund C, Lyko F. Epigenetic cancer therapy: proof of concept and remaining challenges. Bioessays. 2010;32(11):949–57.PubMedGoogle Scholar
  172. 172.
    Miranda TB, Cortez CC, Yoo CB, Liang G, Abe M, Kelly TK, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther. 2009;8(6):1579–88.PubMedPubMedCentralGoogle Scholar
  173. 173.
    Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 2007;21(9):1050–63.PubMedPubMedCentralGoogle Scholar
  174. 174.
    Hur W, Rhim H, Jung CK, Kim JD, Bae SH, Jang JW, et al. SOX4 overexpression regulates the p53-mediated apoptosis in hepatocellular carcinoma: clinical implication and functional analysis in vitro. Carcinogenesis. 2010;31(7):1298–307.PubMedGoogle Scholar
  175. 175.
    Matheu A, Collado M, Wise C, Manterola L, Cekaite L, Tye AJ, et al. Oncogenicity of the developmental transcription factor Sox9. Cancer Res. 2012;72(5):1301–15.PubMedPubMedCentralGoogle Scholar
  176. 176.
    Zhu Y, Li Y, Jun Wei JW, Liu X. The role of Sox genes in lung morphogenesis and cancer. Int J Mol Sci. 2012;13(12):15767–83.PubMedPubMedCentralGoogle Scholar
  177. 177.
    Andreucci E, Pietrobono S, Peppicelli S, Ruzzolini J, Bianchini F, Biagioni A, et al. SOX2 as a novel contributor of oxidative metabolism in melanoma cells. Cell Commun Signal. 2018;16(1):87.PubMedPubMedCentralGoogle Scholar
  178. 178.
    Bhattaram P, Muschler G, Wixler V, Lefebvre V. Inflammatory cytokines stabilize SOXC transcription factors to mediate the transformation of fibroblast-like synoviocytes in arthritic disease. Arthritis Rheum. 2018;70(3):371–82.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Rutgers Cancer Institute of New JerseyNew BrunswickUSA
  2. 2.Department of Radiation OncologyRobert Wood Johnson Medical SchoolNew BrunswickUSA
  3. 3.Rutgers, The State University of New JerseyNew BrunswickUSA

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