TGFβ Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis

Figure 2

TGFβ signaling in epithelial-to-mesenchymal transition. TGFβ signaling mediated by Smad or non-Smad pathways can directly or indirectly induce the expression of different transcriptional “master regulators” of epithelial-to-mesenchymal transition. These factors, including Snail, Slug, ZEB1/delta EF1, and ZEB2/SIP1 are able to initiate a coordinated transcriptional network which results in suppression of epithelial and upregulation mesenchymal marker expression. As a result, epithelial cancer cells undergo dissolution of adherens and tight junctions along with dramatic remodeling of their cytoskeleton and acquire mesenchymal features. These fibroblast-like, spindle shaped tumor cells exhibit significantly enhanced migratory and invasive potential which allows them to enter the blood circulation through the basement membrane and initiate their metastatic dissemination to distal organs.