Abstract IA24: Acetyl-CoA metabolism, gene regulation, and stress management

Acetyl-CoA plays crucial roles at the interface of cellular metabolism, signaling, and epigenetics. This central metabolite is required for de novo biosynthesis of macromolecules such as fatty acids and cholesterol, and it is produced from catabolism of glucose, amino acids, and fatty acids. In addition to its direct metabolic functions, acetyl-CoA serves as the acetyl group donor for both lysine and N-terminal acetylation. Acetyl-CoA availability directly impacts overall histone acetylation levels and participates in gene regulation. In particular, high acetyl-CoA promotes a pro-proliferative gene expression pattern in cancer cells. Diverse signaling and microenvironmental cues impact acetyl-CoA production and utilization, which may influence the ability of cancer cells both to survive in stressful conditions and to grow and proliferate.In human prostate cancer, both fatty acid synthesis and oxidation have been implicated in tumor growth and proposed as therapeutic targets. Moreover, histone acetylation levels are highly correlated with activation of the PI3K-AKT pathway in human prostate tumors and are predictive of patient outcome. We hypothesized that proper coordination of acetyl-CoA production and utilization is central to the ability of prostate cancer cells to survive and proliferate. In this presentation, I will discuss new data on the role of ATP-citrate lyase in coordinating metabolism, gene expression, and oncogenic signaling to balance stress responses and promot...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Metabolic Effects on Epigenetics and Gene Expression: Oral Presentations - Invited Abstracts Source Type: research