Epithelial mesenchymal transition (EMT) in prostate growth and tumor progression.

Abstract

Epithelial-mesenchymal transition (EMT) and its reversal, mesenchymal-epithelial transition (MET), are essential morphological processes during development and in the regulation of stem cell pluripotency, yet these processes are also activated in pathological contexts, such as in fibrosis and cancer progression. Multi-component signaling pathways cooperate in initiation of EMT and MET programs, via transcriptional, post-transcriptional, translational, and post-translational regulation. EMT is required for tissue regeneration and normal embryonic development as it enables epithelial cells to acquire the mesenchymal phenotype, conferring them migratory and dynamic properties towards forming three-dimensional structures during gastrulation and organ formation. Uncontrolled activation of such phenomenon and the pathways signaling EMT events in adult life, leads to cancer growth and orchestrated by signaling interactions from the microenvironment, epithelial tumor cells with enhanced polarity, become invasive and rapidly metastasize to distant sites. Loss of epithelial markers (E-cadherin) and gain of mesenchymal markers (N-cadherin), at the leading edge of solid tumors is associated with progression to metastasis. This review will explore the contribution of EMT to embryonic development of GU organs and the functional consequences of EMT-MET cycles in prostate tumorigenesis. Recent insights identifying key players driving EMT and its reversal to MET during prostate cancer progression to metastatic castration-resistant disease will be discussed, with specific focus on androgen receptor (AR) and transforming growth factor-β (TGF-β) signaling in the context of their predictive and targeting value in prostate cancer progression.