Changes in gene expression in mouse prostate in response to genetic activation of AMPK

Emerging evidence indicates that metabolic dysregulation drives prostate cancer (PCa) progression and metastasis. AMPK is a master regulator of metabolism although its role in PCa remains unclear. Here we show that genetic and pharmacological activation of AMPK provides a dramatic protective effect on PCa progression in vivo. We show that AMPK activation induces PGC1a expression leading to a catabolic metabolic reprogramming of PCa cells. This catabolic state is characterised by increased mitochondrial gene expression, increased fatty acid oxidation, decreased lipogenic potential, decreased cell proliferation and decreased cell invasiveness. Together, these changes inhibit PCa disease progression. Additionally, we identify a gene network that is inhibited by AMPK activation involved in cell cycle regulation. We show correlation between this gene network and PGC1a expression in human PCa. Taken together our findings strongly support the use of AMPK activators for clinical treatment of PCa. Overall design: RNA from six replicate mouse whole prostate tissue from prostate-specific Pten null and prostate-specific Pten null with AMPK gain-of-function (GoF) mutation was sequenced using NextSeq 500.