Androgen control of lipid metabolism in prostate cancer: novel insights and future applications

Abstract

One of the most typical hallmarks of prostate cancer cells is their exquisite dependence on androgens, which is the basis of the widely applied androgen deprivation therapy. Among the variety of key cellular processes and functions that are regulated by androgens, lipid metabolism stands out by its complex regulation and its many intricate links with cancer cell biology. Here, we review our current knowledge on the links between androgens and lipid metabolism in prostate cancer, and highlight recent developments and insights into the links between key oncogenic stimuli and altered lipid synthesis and/or uptake that may hold significant potential for biomarker development and provide new vulnerabilities for therapeutic intervention.

Glycosylation is a global target for androgen control in prostate cancer cells

“…Our approach produced a comprehensive map of 700 genes controlled by the AR in clinical prostate cancer and provides a new window through which to understand the signalling pathways downstream of the AR . Gene set enrichment analysis of these 700 genes identified known AR-regulated processes including fatty acid metabolism (Swinnen et al 1997a, Liu 2006), response to endoplasmic reticulum stress (Segawa et al 2002, Sheng et al 2015 and cholesterol and lipid biosynthesis (Swinnen et al 1997b, Suburu & Chen 2012, Wu et al 2014, Butler et al 2016. In addition to these well-characterised AR-regulated pathways, our data highlighted 'glycosylation' as a previously unidentified global target for androgen control in prostate cancer cells .…”

Identification of response pathways of prostate cancer cell lines in Hans Clevers Media

“…Androgen and insulin share regulatory control of numerous pathways including lipid metabolism (Butler et al, 2016;Saltiel et al, 2016). Pathway analysis identified lipid metabolism pathways in both the HCM and androgen-enriched RPMI VCaP cells suggesting the androgen-like effects of HCM could potential be explained by the presence of insulin in HCM.…”

“…Lipid metabolism is strikingly affected by androgens and lipid metabolism dysregulation is a key feature of PCa development (Butler et al, 2016;Wu, Daniels, Lee, & Monaco, 2014). As lipid metabolism is regulated by androgens, lipids have the potential to be effected by elements in certain media systems that would regulate the AR.…”

“…Androgens drive lipid metabolism primarily through the promotion of de novo lipogenesis and fatty acid (FA) uptake (Butler et al, 2016). Most metabolized cellular FA are either synthesized into neural triglycerides (TAG) for energy storage within LDs or into phospholipids for cell/organelle membrane growth or maintenance.…”

“…Although androgens have a profound effect on lipid metabolism, other molecules such as insulin are also key regulators of lipid metabolism (Butler et al, 2016;Wu, Daniels, Lee, & Monaco, 2014;Wuttke et al, 2015).…”