Histone lysine demethylase inhibition reprograms prostate cancer metabolism and mechanics.

ABSTRACT:

Objective

Aberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced PCa. Although direct AR signaling inhibitors exist, AR expression and function can also be epigenetically regulated. Specifically, lysine (K)-specific demethylases (KDMs), which are often overexpressed in PCa and CRPC phenotypes, regulate the AR transcriptional program.

Methods

We investigated LSD1/UTX inhibition, two KDMs, in PCa and CRPC using a multi-omics approach. We first performed a mitochondrial stress test to evaluate respiratory capacity after treatment

SUBMITTER: Chianese U 

PROVIDER: S-EPMC9403566 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature