title: SOX10 is a novel oncogene in hepatocellular carcinoma through Wnt/β-catenin/TCF4 cascade.
abstract: SOX (high mobility group) genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the function role of SOXs in the human hepatocellular carcinoma (HCC). The gene expression changes of SOXs in HCC tissues compared with those in noncancerous hepatic tissues were detected using real-time quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry. In addition, we identified the gene SOX10 that was significantly upregulated in HCC by QRT-PCR analysis and immunohistochemistry. Furthermore, we discovered that SOX10 promoted cancer cell proliferation in vitro, and SOX10 expression correlated with elevated β-catenin levels in HCC, and β-catenin function was required for SOX10's oncogenic effects. Mechanistically, SOX10 facilitates TCF4 to bind to β-catenin and form a stable SOX10/TCF4/β-catenin complex and trans-activate its downstream target gene. SOX10 mutations that disrupt the SOX10-β-catenin interaction partially prevent its function in tumor cells. All in all, SOX10 is a commonly activated tumor promoter that activates Wnt/β-catenin signaling in cancer cells of HCC.
authors.affiliation: Department of Surgical Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
authors.forename: Dangjun
authors.initials: D
authors.lastname: Zhou
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Bai
authors.forename: Xinning
authors.initials: X
authors.lastname: Zhang
authors.forename: Minggen
authors.initials: M
authors.lastname: Hu
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhao
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055757:SOXE Transcription Factors / Q000235:genetics*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D059467:Transcriptome; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin