TGF-β signaling networks in the tumor microenvironment.

Transforming growth factor-β (TGF-β) signaling shows important roles in both physiology and pathology, especially in the progression of inflammatory diseases including cancer. Interestingly, TGF-β was first reported as a cancer suppressor, but increasing evidence confirmed its protumoral actions. Paradoxically, TGF-β can be produced by both cancer cells and stromal cells as a signaling network, which actively shapes the tumor microenvironment (TME). Surprisingly, disruption of TGF-β signaling results in both anti-cancer and pro-tumoral phenotypes in experimental cancer models, revealing the unexpected complexity of its downstream pathways for mediating cancer progression. Thus, a better understanding of the underlying mechanisms of TGF-β signaling at the molecular level can bring new insights for developing medications that can precisely separate the anti-cancer actions from the tumor-promoting outcomes. Here, we systematically summarized the latest discoveries of TGF-β signaling in cancer cells and the TME and discussed their translational implications for cancer.