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

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.

Integrin α7: a major driver and therapeutic target for glioblastoma malignancy

“…A similar role for integrin α7 has been described in oesophageal squamous carcinoma stem cells as a high incidence of integrin α7-positive cells in oesophageal squamous cell carcinoma tissues result in increased lymph node metastasis and worse patient prognosis (17). Interestingly, the role of integrin α7 in proliferation and migration has been described in other cell types including muscle cells.…”

ITGA2is a target of miR-206 promoting cancer stemness and lung metastasis through enhancedACLYandCCND1expression in triple negative breast cancer

“…FAK, a non-receptor tyrosine kinase is activated by CD49b signaling and has been identified as a key mediator of intracellular signaling by integrins 33,34 . Several other integrins have also been identified as markers of cancer stem cells, such as CD49f (integrin α6), integrin α7, and CD104 (integrin-β4) [35][36][37] . Both integrins and FAK can play crucial roles in the maintenance of breast cancer stem cells 26,38 .…”

Glioblastoma stem cells exploit the αvβ8 integrin-TGFβ1 signaling axis to drive tumor initiation and progression

“…67 For example, tumor-initiating cells isolated from breast adenocarcinomas express αvβ3 integrin 68 and cancer stem cells fractionated from esophageal squamous carcinomas express α7β1 integrin. 69 Although integrins are used primarily as biomarkers for tumor-initiating cells, they are likely providing critical ECM adhesion functions. Hence, therapeutically targeting integrins may be beneficial for blocking cancer stem cell interactions with ECM ligands in their niche to inhibit tumor growth and progression.…”