This study delineates the novel spatiotemporal regulation of initiation and progression of cancer cells, where the initial step of the acquisition of EMT is most likely regulated by TGF-β produced by the tumor microenvironment, and in the process of subsequent cancer progression, a novel collaboration between TGF-β and Crk forms a positive feedback loop that may play a role especially at the invasive front of cancers. The gene discussed is TGFB1; the disease is cancer.