EZH2 通过调节人口腔鳞状细胞癌细胞中的 STAT3 和 FoxO1 信号通路促进侵袭和肿瘤糖酵解。

EZH2 promotes invasion and tumour glycolysis by regulating STAT3 and FoxO1 signalling in human OSCC cells.

机构信息

Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

出版信息

J Cell Mol Med. 2019 Oct;23(10):6942-6954. doi: 10.1111/jcmm.14579. Epub 2019 Jul 31.

The enhancer of zeste homolog 2 (EZH2), known as a member of the polycomb group (PcG) proteins, is an oncogene overexpressed in a variety of human cancers. Here, we found that EZH2 correlated with poor survival of oral squamous cell carcinoma (OSCC) patients using immunohistochemistry staining. EZH2 overexpression led to a significant induction in tumour glycolysis, Epithelial-mesenchymal transition (EMT), migration and invasion of OSCC cells. Conversely, silencing of EZH2 inhibited tumour glycolysis, EMT, migration and invasion in OSCC cells. Ectopic overexpression of EZH2 increased phosphorylation of STAT3 at pY705 and decreased FoxO1 expression, and FoxO1 expression was enhanced when inhibiting STAT3. In addition, EZH2 overexpression led to a significant decrease in FoxO1 mRNA levels in nude mice xenograft. These results indicated that regulation of EZH2 might have the potential to be targeted for OSCC treatment.

增强子结合锌指蛋白 2（EZH2），作为多梳抑制复合物（PcG）蛋白家族的一员，在多种人类癌症中过表达。在这里，我们发现免疫组织化学染色显示 EZH2 与口腔鳞状细胞癌（OSCC）患者的不良生存相关。EZH2 的过表达导致 OSCC 细胞中肿瘤糖酵解、上皮-间充质转化（EMT）、迁移和侵袭显著增加。相反，EZH2 的沉默抑制了 OSCC 细胞中的肿瘤糖酵解、EMT、迁移和侵袭。EZH2 的异位过表达增加了 STAT3 在 pY705 处的磷酸化并降低了 FoxO1 的表达，而抑制 STAT3 则增强了 FoxO1 的表达。此外，EZH2 的过表达导致裸鼠异种移植中 FoxO1mRNA 水平显著降低。这些结果表明，EZH2 的调控可能具有成为 OSCC 治疗靶点的潜力。