1. Integrin α7 is a functional cancer stem cell surface marker in oesophageal squamous cell carcinoma
- Author
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Stephanie Ma, Kwok Wah Chan, Dan Xie, Li Fu, Xiao Yan Ming, Yan Ru Qin, Xin Yuan Guan, Ting Ting Cao, and Li Yi Zhang
- Subjects
0301 basic medicine ,Esophageal Neoplasms ,Science ,Integrin ,Transplantation, Heterologous ,General Physics and Astronomy ,Mice, SCID ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Cancer stem cell ,Antigens, CD ,Mice, Inbred NOD ,Cell Line, Tumor ,Carcinoma ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Regulation of gene expression ,Gene knockdown ,Multidisciplinary ,biology ,General Chemistry ,medicine.disease ,Embryonic stem cell ,Tumor Burden ,Transplantation ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,030104 developmental biology ,Cell culture ,Lymphatic Metastasis ,Cancer research ,biology.protein ,Carcinoma, Squamous Cell ,Neoplastic Stem Cells ,RNA Interference ,Integrin alpha Chains - 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., There is still no consensus on tumour type-specific cancer stem cell markers. Here, the authors demonstrate that ITGA7 is a potential functional marker of oesophageal cancer stem cells involved in the resistance to chemotherapy and metastasis through activation of FAK-mediated signalling.
- Published
- 2016