Abstract
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.
Highlights
Non-CG methylation has been associated with stemness regulation in embryonic stem cells
Expression of Integrin a7 (ITGA7) was analyzed by immunohistochemistry (IHC) on a tissue microarray (TMA) consisting of 300 paired oesophageal squamous cell carcinoma (OSCC) and non-tumour clinical samples
Kaplan–Meier survival analysis based on this TMA data found that OSCC patients with high frequency of ITGA7 þ cells (40.6%) were significantly associated with a shorter survival time
Summary
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 a7 (ITGA7) is characterized as a potential cancer stem cell (CSC) marker. We first selected 10 stemness-associated genes with differential non-CG methylation between ESC and fibroblast from Lister et al.’s report for preliminary study in OSCC cell lines and clinical specimens. Recent studies have suggested that integrins play important roles in the regulation of stem cell-like properties and enrich CSCs from glioblastoma multiforme (GBM)[19], breast cancer[20] and prostate cancer[21]. Functional studies demonstrate that ITGA7 þ cells possess strong CSC properties including abilities to self-renew, differentiate and resist chemotherapy. Our data indicate that ITGA7 is a potential CSC marker in OSCC with function in stemness regulation
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