SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β-catenin pathway.

Autor: Xie SL; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Fan S; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Zhang SY; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China., Chen WX; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Li QX; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Pan GK; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Zhang HQ; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Wang WW; Department of Stomatology, Zibo Center Hospital, Zibo, China., Weng B; Department of Pathology, The Affiliated Hospital of North Sichuan Medical College, Nanchong, China., Zhang Z; Department of Pathology, West China Hospital, Sichuan University, Chengdu, China., Li JS; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China., Lin ZY; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2018 Mar 15; Vol. 142 (6), pp. 1252-1265. Date of Electronic Publication: 2017 Nov 06.
DOI: 10.1002/ijc.31134
Abstrakt: 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.
(© 2017 UICC.)
Databáze: MEDLINE
Externí odkaz: