Integrin α7 is a functional cancer stem cell surface marker in oesophageal squamous cell carcinoma

• DOI: 10.1038/ncomms13568
• Publication Date: 2016-12-07T11:31:01Z
• Authors: Xiao-Yan Ming; Li Fu; Li-Yi Zhang; Yan-Ru Qin; Ting-Ting Cao; Kwok Wah Chan; Stephanie Ma; Dan Xie; Xin-Yuan Guan
• Keywords: 0301 basic medicine; Esophageal Neoplasms; Science; Q; Transplantation, Heterologous; Mice, SCID; Article; Tumor Burden; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Antigens, CD; Mice, Inbred NOD; Cell Line, Tumor; Lymphatic Metastasis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Neoplastic Stem Cells; Animals; Humans; RNA Interference; Integrin alpha Chains

AbstractNon-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.