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

Transforming growth factor-beta (TGF-beta) is a member of a family of secreted cytokines with vital biological functions in cells. The abnormal expression of TGF-beta 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-beta signaling in PCa. TGF-beta 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-beta signaling via induction of EMT and MMPs. Furthermore, TGF-beta 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-beta signaling in PCa. Furthermore, some pharmacological compounds such as thymoquinone and valproic acid can suppress TGF-beta signaling for PCa therapy. TGF-beta over-expression is associated with poor prognosis in PCa patients. Furthermore, TGF-beta up regulation before prostatectomy is associated with recurrence of PCa. Overall, current review discusses role of TGF-beta signaling in proliferation, metastasis and therapy response of PCa cells and in order to improve knowledge towards its regulation, upstream mediators of TGF-beta such as non-coding RNAs are described. Finally, TGF-beta regulation and its clinical application are discussed.

Automated summary

This review discusses the role of TGF-beta signaling in the proliferation, metastasis, and therapy response of prostate cancer cells. It also explores the regulation of TGF-beta signaling and its clinical application.