aV integrins and TGF-ß-induced EMT: a circle of regulation

Transforming growth factor-beta (TGF-beta) has roles in embryonic development, the prevention of inappropriate inflammation and tumour suppression. However, TGF-beta 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-beta 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 aV integrins and TGF-beta during EMT, and anti-integrin therapeutics are under development as treatments for TGF-beta-related disorders. However, TGF-beta s complex signalling network makes the development of therapeutics to block TGF-beta-mediated pathology challenging. Moreover, despite our current understanding of integrins and TGF-beta 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 aV integrin and TGF-beta signalling during TGF-beta induced EMT, which pose as a significant driver to many known TGF-beta-mediated disorders.