The role of hypoxia on prostate cancer progression and metastasis.

Prostate cancer is the second most common cancer diagnosed in men and the fifth-leading cause of cancer death in men worldwide. Like any solid tumor, the hypoxic microenvironment of prostatic cancer drives hypoxia-inducible factors (HIFs) to mediate cell adaptions to hypoxic conditions. HIFs direct different signaling pathways such as PI3K/Akt/mTOR, NOX, and Wnt/β-Catenin to tumor progression depending on the degree of hypoxia. HIFs regulate cytoskeleton protein expression, promoting epithelial-mesenchymal transition (EMT), which occurs when cancer cells lose cell-to-cell adhesions and start invasion and metastasis. Through activating pathways, the hypoxic microenvironment maintains the self-renewal, potency, and anti-apoptotic function of prostate cancer cells and induces tumor metastasis and transformation. These pathways could serve as a potential target for prostate cancer therapy. HIFs increase the expression of androgen receptors on cancer cells maintaining the growth and survival of prostate cancer and the development of its castration resistance. In this review, we elaborate on the role of hypoxia in prostatic cancer pathogenesis and different hypoxia-induced mechanisms.