Figure 6. Schematic of the signaling mechanism of collaboration between TGF-β and Crk to induce EMT in human cancer cells.

TGF-β initially produced by cancer-associated fibroblasts may enhance expression of CrkI and CrkII, which leads to activation of Rac1 and RhoA to increase the levels of EMT regulators Snail and Slug. This leads to a cadherin switch demonstrating a decrease in E-cadherin and increase in N-cadherin expression, concurrent with MMP2 activation, resulting in the induction of EMT. Upregulation of CrkI- and CrkII-induced TGF-β production and its receptor in cancer cells forms a positive feedback loop for malignant progression.