Suppression of premature senescence and promotion of metastatic transformation: Role of reduced TGF-Beta signaling in human cancer progression

Transforming growth factor-beta (TGF-β) signaling pathway serves as a tumor suppressor by inhibiting cell cycle progression and stimulating senescence and apoptosis in normal and early-stages neoplastic tissues. As tumors progress, TGF-β signaling is often turned to drive multi-step metastasis processes by stimulating cell survival and epithelial-tomesenchymal transition (EMT) leading to tumor cell migration and invasion. Many human carcinomas including triple-negative breast cancer, often show reduced or loss of key components of TGF-β signaling, indicating reduced tumor-suppressive TGF-β signaling may contribute to the cancer progression. However, molecular mechanisms that drive the switch of TGF-β are not well understood. Few molecular biomarkers have been identifi ed as effi cient indicators for the anti-TGF-β cancer therapy. In order to better understand the mechanism mediating the role of TGF-β during cancer progression, we will discuss the question of how the loss of control of cell proliferation and senescence by TGF-β promotes tumor invasion and metastasis and whether a set of transformation/metastasis-related genes are specifi cally regulated by TGF-β signaling.