Transforming growth factor‐β signaling: Tumorigenesis and targeting for cancer therapy.

Transforming growth factor (TGF)‐β is a multitasking cytokine such that its aberrant expression is related to cancer progression and metastasis. TGF‐β is produced by a variety of cells within the tumor microenvironment (TME), and it is responsible for regulation of the activity of cells within this milieu. TGF‐β is a main inducer of epithelial–mesenchymal transition (EMT), immune evasion, and metastasis during cancer progression. TGF‐β exerts most of its functions by acting on TβRI and TβRII receptors in canonical (Smad‐dependent) or noncanonical (Smad‐independent) pathways. Members of mitogen‐activated protein kinase, phosphatidylinositol 3‐kinase/protein kinase B, and nuclear factor κβ are involved in the non‐Smad TGF‐β pathway. TGF‐β acts by complex signaling, and deletion in one of the effectors in this pathway may influence the outcome in a diverse way by taking even an antitumor role. The stage and the type of tumor (contextual cues from cancer cells and/or the TME) and the concentration of TGF‐β are other important factors determining the fate of cancer (progression or repression). There are a number of ways for targeting TGF‐β signaling in cancer, among them the special focus is on TβRII suppression. [ABSTRACT FROM AUTHOR]