SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway. Issue 6 (6th November 2017)

• Record Type: Journal Article
• Authors: Xie, S.‐L.; Fan, S.; Zhang, S.‐Y.; Chen, W.‐X.; Li, Q.‐X.; Pan, G.‐K.; Zhang, H.‐Q.; Wang, W.‐W.; Weng, B.; Zhang, Z.; Li, J.‐S.; Lin, Z.‐Y.
• Is Part Of: International journal of cancer. Volume 142:Issue 6(2018)
• Page Start: 1252
• Page End: 1265
• Publication Date: 2017-11-06
• Subjects: Cancer stem cell -- SOX transcription factors -- EMT -- cisplatin resistance -- Wnt/β‐catenin pathway -- tongue squamous cell carcinoma; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31134
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : A sub‐population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin‐resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin‐resistant TSCC cells, which displayed CSC‐like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin‐resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/β‐catenin pathway mediated the cancer stem‐like properties in cisplatin‐resistant TSCC cells. Further studies showed that the transfection of active β‐catenin in SOX8 stable‐knockdown cells partly rescued the SOX8 silencing‐induced repression of stem‐like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled‐7 (FZD7) and induced the FZD7‐mediated activation of the Wnt/β‐catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7‐mediated Wnt/β‐catenin pathway. Abstract : What's new? Tongue cancer frequently spreads to the lymph nodes, and while chemotherapy with cisplatin has improved 5‐year survival rates, all too often the cancer becomes resistant to chemotherapy and returns. Here, the authors show that tongue squamous cell carcinoma (TSCC) cells that have acquired cisplatin resistance express more SOX‐8 mRNA than their parent TSCC cells. Getting rid of SOX‐8, they showed, hampered the cells' chemoresistance as well as the epithelial to mesenchymal transition. Adding active beta‐catenin to the cells lacking SOX‐8 partially restored these properties, showing that SOX‐8 acts through the Wnt/beta‐catenin pathway.