Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 852, China.
Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 852, China.
Nat Commun. 2016 Dec 7;7:13568. doi: 10.1038/ncomms13568.
Non-CG methylation has been associated with stemness regulation in embryonic stem cells. By comparing differentially expressed genes affected by non-CG methylation between tumour and corresponding non-tumour tissues in oesophageal squamous cell carcinoma (OSCC), we find that Integrin α7 (ITGA7) is characterized as a potential cancer stem cell (CSC) marker. Clinical data show that a high frequency of ITGA7 cells in OSCC tissues is significantly associated with poor differentiation, lymph node metastasis and worse prognosis. Functional studies demonstrate that both sorted ITGA7 cells and ITGA7 overexpressing cells display enhanced stemness features, including elevated expression of stemness-associated genes and epithelial-mesenchymal transition features, as well as increased abilities to self-renew, differentiate and resist chemotherapy. Mechanistic studies find that ITGA7 regulates CSC properties through the activation of the FAK-mediated signalling pathways. As knockdown of ITGA7 can effectively reduce the stemness of OSCC cells, ITGA7 could be a potential therapeutic target in OSCC treatment.
非 CG 甲基化与胚胎干细胞中的干性调节有关。通过比较食管鳞状细胞癌(OSCC)中肿瘤和相应非肿瘤组织中非 CG 甲基化对差异表达基因的影响,我们发现整合素α7(ITGA7)是一种潜在的癌症干细胞(CSC)标志物。临床数据表明,OSCC 组织中 ITGA7 细胞的高频率与分化不良、淋巴结转移和预后不良显著相关。功能研究表明,分选的 ITGA7 细胞和过表达 ITGA7 的细胞均表现出增强的干性特征,包括干细胞相关基因和上皮-间充质转化特征的上调,以及自我更新、分化和抵抗化疗能力的增强。机制研究发现,ITGA7 通过激活 FAK 介导的信号通路来调节 CSC 特性。由于 ITGA7 的敲低可有效降低 OSCC 细胞的干性,因此 ITGA7 可能成为 OSCC 治疗的潜在治疗靶点。