Overexpression of REST Represses the Epithelial-Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells.

Abstract

The RE-1 silencing transcription factor (REST) is a repressor factor related to neuroendocrine prostate cancer (PCa) (NEPC), a poor prognostic stage mainly associated with castration-resistant PCa (CRPC). NEPC is associated with cell transdifferentiation and the epithelial-mesenchymal transition (EMT) in cells undergoing androgen deprivation therapy (ADT) and enzalutamide (ENZ). The effect of REST overexpression in the 22rv1 cell line (xenograft-derived prostate cancer) on EMT, migration, invasion, and the viability for ENZ was evaluated. EMT genes, Twist and Zeb1, and the androgen receptor (AR) were evaluated through an RT-qPCR and Western blot in nuclear and cytosolic fractions of REST-overexpressing 22rv1 cells (22rv1-REST). The migratory and invasive capacities of 22rv1-REST cells were evaluated via Transwell® assays with and without Matrigel, respectively, and their viability for enzalutamide via MTT assays. The 22rv1-REST cells showed decreased nuclear levels of Twist, Zeb1, and AR, and a decreased migration and invasion and a lower viability for ENZ compared to the control. Results were expressed as the mean + SD of three independent experiments (Mann-Whitney U test, Kruskal-Wallis, Tukey test). REST behaves like a tumor suppressor, decreasing the aggressiveness of 22rv1 cells, probably through the repression of EMT and the neuroendocrine phenotype. Furthermore, REST could represent a response marker to ENZ in PCa patients.

• Authors: Sebastián Indo, Octavio Orellana-Serradell, María José Torres, Enrique A Castellón, Héctor R Contreras
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 25 Issue 6 (Mar 15 2024) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 38542313 (Publication Type: Journal Article)

Chemical References

• enzalutamide
• Androgen Antagonists
• Transcription Factors
• Receptors, Androgen
• Benzamides
• Nitriles
• Phenylthiohydantoin

Topics

• Male
• Humans
• Prostatic Neoplasms (metabolism)
• Androgen Antagonists
• Transcription Factors
• Cell Line, Tumor
• Receptors, Androgen (metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Prostatic Neoplasms, Castration-Resistant (pathology)
• Benzamides
• Nitriles
• Phenylthiohydantoin