Fig. 2.

Contribution of integrin-mediated TGFβ1 activation of pro-tumour mechanisms via regulation of cells of the immune system, promotion of epithelial-mesenchymal transition and angiogenesis. Immune system 1) Active TGFβ stimulates naive T-cell-to-Treg differentiation (top). Tregs exhibit αvβ8-mediated TGFβ1 activation, amplifying the differentiation of other naive T-cells. Tregs suppress anti-tumour T-cell responses. Tumour cell integrins mediate TGFβ1 activation (bottom). Active TGFβ1 stimulates macrophage and neutrophil pro-tumour responses. Epithelial-to-mesenchymal transition TGFβ1 stimulation of epithelial cells represses epithelial gene signatures, e.g., cell-cell adhesion molecule E-cadherin (top). This promotes a more mesenchymal invasive cell phenotype (bottom). Angiogenesis TGFβ1 stimulation of tumour cells increases VEGF expression, which binds to its receptor on local endothelial cells. Integrin αvβ3 promotes activation and recycling of VEGFR (left). The αvβ8-mediated activation of TGFβ1 facilitates TGFβ activation of local endothelial cells, which can promote or inhibit angiogenesis via separate TGFβ receptors (right)