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Figure. The role of TGF-ß in epithelial carcinogenesis. In normal epithelial cells with an intact TGF-ß signaling pathway, TGF-ß functions as a tumor suppressor by inhibiting cell proliferation and enhancing apoptosis, together with the regulation of replicative senescence and suppression of telomerase. During multi-step tumorigenesis, cells acquire defects in the TGF-ß signaling pathway, which abrogates or diminishes the responses of the tumor cells to TGF-ß, and oncogene signaling may also alter the cellular response to TGF-ß. Some late-stage tumors are also known to overproduce TGF-ß. Consequently, TGF-ß shifts from a suppressor to a promoter of tumor progression, by increasing angiogenesis, enhancing motility/invasion, and, at times, inducing an epithelial-mesenchymal transdifferentiation.
