Human malignancies frequently exhibit mutations in the TGF-β pathway, and overactivation of this system is linked to tumor growth by promoting angiogenesis and inhibiting the innate and adaptive antitumor immune responses.
Anti-inflammatory cytokine.
In normal tissues, TGF-β plays an essential role in cell cycle regulation, immune function, and tissue remodeling.
- In early carcinogenesis, TGF-β typically acts as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis.
In advanced cancers, cells frequently become resistant to the growth-inhibitory effects of TGF-β.
- TGF-β then switches roles and promotes tumor progression by stimulating epithelial-to-mesenchymal transition (EMT), cell invasion, metastasis, and immune evasion.
Non-canonical (Smad-independent) pathways, such as MAPK, PI3K/Akt, and Rho signaling, also contribute to TGF-β-mediated responses.
Elevated levels of TGF-β have been detected in many advanced-stage cancers, including breast, lung, colorectal, pancreatic, and prostate cancers.
- The switch from a tumor-suppressive to a tumor-promoting role is often associated with increased TGF-β production and activation in the tumor microenvironment.
High TGF-β expression or signaling activity is frequently correlated with aggressive disease features, resistance to therapy, increased metastasis, and poorer overall survival in many cancer types.
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