SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β-catenin pathway
SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β-catenin pathway
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SOX8 通过作用于 Wnt/b-catenin 通路调节舌鳞状细胞癌中的癌症干细胞样特性和顺铂诱导的 EMT
DOI：
10.1002/ijc.31134
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发表时间：
2018-03-15
影响因子：
6.4
通讯作者：
Lin, Z. -Y.
中科院分区：
文献类型：
--
作者：
Xie, S. -L.;Fan, S.;Lin, Z. -Y.
化疗耐药细胞亚群表现出与癌症干细胞（CSC）相似的生物学特性，这些细胞被认为是肿瘤复发和转移的主要原因。在我们的研究中，我们探讨了SOX8在顺铂耐药舌鳞状细胞癌（TSCC）细胞干细胞特性和上皮间质转化（EMT）调节中的作用及其分子机制。我们发现 SOX8 在顺铂耐药的 TSCC 细胞中表达上调，这些细胞表现出 CSC 样特性并表现出 EMT。 SOX8 在化疗耐药的 TSCC 患者中也过度表达，并且与较高的淋巴结转移、晚期肿瘤分期和较短的总生存期相关。在顺铂耐药的 TSCC 细胞中稳定敲低 SOX8 可抑制化疗耐药、肿瘤球形成和 EMT。 Wnt/-catenin 通路介导顺铂耐药 TSCC 细胞中的癌症干细胞样特性。进一步的研究表明，在SOX8稳定敲低细胞中转染活性β-连环蛋白可以部分挽救SOX8沉默引起的干细胞样特征和化疗耐药性的抑制。通过染色质免疫沉淀和荧光素酶测定，我们观察到 SOX8 与 Frizzled-7 (FZD7) 的启动子区域结合，并诱导 FZD7 介导的 Wnt/-catenin 通路激活。总之，SOX8 赋予化疗耐药性和干性特性，并通过 FZD7 介导的 Wnt/-catenin 途径介导化疗耐药 TSCC 中的 EMT 过程。
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/-catenin pathway mediated the cancer stem-like properties in cisplatin-resistant TSCC cells. Further studies showed that the transfection of active -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/-catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7-mediated Wnt/-catenin pathway.