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

Transforming growth factor (TGF)- is a multitasking cytokine suchthat its aberrant expression is related to cancer progression and metastasis. TGF- 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- is a main inducer of epithelial-mesenchymal transition (EMT), immune evasion, and metastasis during cancer progression. TGF- exerts most of itsfunctions by acting on TRI and TRII 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 are involved in the non-Smad TGF- pathway. TGF- acts bycomplex 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- are other important factors determining the fate of cancer (progression or repression). There are a number of ways for targeting TGF- signaling in cancer, among them the special focus is on TRII suppression.