aV integrins and TGF‐β‐induced EMT: a circle of regulation

Abstract EMT and pathogenesis: the good, the bad and the ugly TGF‐b—a central player in EMT Changes in cell–cell/cell–ECM adhesion in EMT—the role of integrins during EMT TGF‐b as a regulator of integrin expression during EMT aV integrins activate TGF‐b ‐ Conformational change activation mechanism ‐ Conformational change activation mechanism with proteolysis TGF‐b and integrin signalling cross‐talk during EMT Disease perspectives Completing the circle Acknowledgements Conflicts of interest Transforming growth factor‐β (TGF‐β) has roles in embryonic development, the prevention of inappropriate inflammation and tumour suppression. However, TGF‐β signalling also regulates pathological epithelial‐to‐mesenchymal transition (EMT), inducing or progressing a number of diseases ranging from inflammatory disorders, to fibrosis and cancer. However, TGF‐β signalling does not proceed linearly but rather induces a complex network of cascades that mutually influence each other and cross‐talk with other pathways to successfully induce EMT. Particularly, there is substantial evidence for cross‐talk between αV integrins and TGF‐β during EMT, and anti‐integrin therapeutics are under development as treatments for TGF‐β‐related disorders. However, TGF‐β’s complex signalling network makes the development of therapeutics to block TGF‐β‐mediated pathology challenging. Moreover, despite our current understanding of integrins and TGF‐β function during EMT, the precise mechanism of their role during physiological versus pathological EMT is not fully understood. This review focuses on the circle of regulation between αV integrin and TGF‐β signalling during TGF‐β induced EMT, which pose as a significant driver to many known TGF‐β‐mediated disorders.