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

• Published in: Nature communications Vol. 7; no. 1; p. 13568
• Main Authors: Ming, Xiao-Yan, Fu, Li, Zhang, Li-Yi, Qin, Yan-Ru, Cao, Ting-Ting, Chan, Kwok Wah, Ma, Stephanie, Xie, Dan, Guan, Xin-Yuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.12.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/105; 13/106; 13/109; 13/2; 13/31; 13/51; 13/89; 38/22; 38/90; 631/67/1504/1477; 692/4028/67/71; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Integrin alpha Chains - genetics; Integrin alpha Chains - metabolism; Lymphatic Metastasis; Mice, Inbred NOD; Mice, SCID; multidisciplinary; Neoplastic Stem Cells - metabolism; RNA Interference; Science; Science (multidisciplinary); Transplantation, Heterologous; Tumor Burden - genetics
• ISSN: 2041-1723; 2041-1723
• 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. 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.