Integrin α3/α6 and αV are implicated in ADAM15-activated FAK and EGFR signalling pathway individually and promote non-small-cell lung cancer progression

Abstract

Abstract Disintegrin-metalloproteinase 15(ADAM15), a member of disintegrin metalloproteinases (ADAMs), plays important roles in various cancer types. However, the underlying ADAM15 functioning in lung cancer is still unclear. In the present study, we find that ADAM15 regulates the epidermal growth factor receptor/focal adhesion kinase (EGFR/FAK) signalling pathway by interactions with integrins. Integrin αV is involved in ADAM15-mediated FAK signalling. Further, we find that ADAM15 and CD151 were co-expressed, and the presence of ADAM15 affected the integrin α3/α6-related EGFR signalling pathway by cooperating with CD151. In addition, we also prove the effect of ADAM15 on proliferation in nude mice. Finally, we show that ADAM15 is a direct target of miR-204-5p by luciferase reporter assays, qRT-PCR and western blot analyses. Our findings provide molecular and cellular evidence that ADAM15 promotes cell proliferation and metastasis in NSCLC, which might provide a potential target for NSCLC treatment.