Transforming growth factor-beta (TGF-β) in prostate cancer: A dual function mediator?

Transforming growth factor-beta (TGF-β) is a member of a family of secreted cytokines with vital biological functions in cells. The abnormal expression of TGF-β signaling is a common finding in pathological conditions, particularly cancer. Prostate cancer (PCa) is one of the leading causes of death among men. Several genetic and epigenetic alterations can result in PCa development, and govern its progression. The present review attempts to shed some light on the role of TGF-β signaling in PCa. TGF-β signaling can either stimulate or inhibit proliferation and viability of PCa cells, depending on the context. The metastasis of PCa cells is increased by TGF-β signaling via induction of EMT and MMPs. Furthermore, TGF-β signaling can induce drug resistance of PCa cells, and can lead to immune evasion via reducing the anti-tumor activity of cytotoxic T cells and stimulating regulatory T cells. Upstream mediators such as microRNAs and lncRNAs, can regulate TGF-β signaling in PCa. Furthermore, some pharmacological compounds such as thymoquinone and valproic acid can suppress TGF-β signaling for PCa therapy. TGF-β over-expression is associated with poor prognosis in PCa patients. Furthermore, TGF-β up-regulation before prostatectomy is associated with recurrence of PCa. Overall, current review discusses role of TGF-β signaling in proliferation, metastasis and therapy response of PCa cells and in order to improve knowledge towards its regulation, upstream mediators of TGF-β such as non-coding RNAs are described. Finally, TGF-β regulation and its clinical application are discussed.