title: Androgen regulation of epithelial-mesenchymal transition in prostate tumorigenesis.
abstract: Prostate cancer patient mortality is ascribed to the spread of cancerous cells to areas outside the prostate gland and the inability of current treatment strategies to effectively block progression to metastasis. Understanding the cellular mechanisms contributing to the dissemination of malignant cells and metastasis is critically significant to the generation of effective therapeutic modalities for improved patient survival while combating therapeutic resistance. In recent years, the phenomenon of epithelial-mesenchymal transitions (EMTs) has received considerable attention due to accumulating evidence indicating a role for this developmentally conserved process in tumorigenesis. Cancer cells at the invasive edges of tumors undergo EMT under the influence of contextual signals that they receive from the microenvironment, such as TGF-β. Also derived from developmental studies is the fact that EMT induction is reversible; thus, upon removal of EMT-inducing signals, cells occasionally revert to the epithelial state of their cellular ancestors via the process of mesenchymal-epithelial transition. This article discusses the current evidence supporting a central role for EMT and its reverse process, mesenchymal-epithelial transition, in the metastatic progression of prostate cancer to advanced disease and the involvement of androgen signaling in its regulation towards the development of castration-resistant prostate cancer.
authors.affiliation: Department of Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536, USA ; Department of Surgery/Urology, University of Kentucky College of Medicine, KY, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Matuszak
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
keywords: EMT; TGF-β; ZEB1/2; androgen axis; androgen receptor; cadherins; metastasis; prostate tumor progression; stem cells; tumor microenvironment; vimentin