Graphical Abstract.

Mechanisms of integrin-mediated transforming growth factor beta (TGFβ) activation and its effect on stromal processes. 1 Matrix-bound latent LAP-TGFβ1 binds αv integrins expressed by epithelial cells or fibroblasts (LAP latency-associated peptide). TGFβ1 becomes exposed. 2 Active TGFβ1 binds the TGFβ receptor in an autocrine or paracrine fashion. 3 TGFβ1 signalling increases integrin expression, LAP-TGFβ1 secretion and trans-differentiation of fibroblasts into contractile cells that secrete collagens and collagen cross-linking proteins. By contracting the matrix, latent TGFβ1 is stretched making the activation of latent TGFβ1 easier and creating a continuous cycle of TGFβ1 signalling. TGFβ1 promotes cancer progression by promoting angiogenesis, immune suppression and epithelial-to-mesenchymal transition (EMT)