Understanding the interplay between amino acid and lipid metabolism in tumor growth

Abstract

Metabolism is central to virtually all cellular functions and contributes to a range of diseases. A quantitative understanding of how biochemical pathways are dysregulated in the context of diseases such as cancer and metabolic syndrome is necessary to identify new therapeutic targets. To this end we apply stable isotope tracers, mass spectrometry, and metabolic flux analysis (MFA) to study metabolism in mammalian cells, animal models, and human patients. Using these approaches we have characterized how proliferating and differentiated cells regulate flux of glucose and amino acids into lipid biosynthetic pathways. We are particularly interested in understanding how amino acid and lipid metabolism are coordinated to meet these needs. Transport of pyruvate into mitochondria is a critical step in these processes, and activity of the mitochondrial pyruvate carrier (MPC) strongly influences cancer growth in vivo and as tumor spheroids. Using metabolomics and lipidomics approaches we have identified mechanisms through which MPC flux and amino acid availability impact sphingolipid metabolism. Modulation of these pathways influences tumor growth, providing mechanistic insights into how amino acid metabolism can influence lipids and mitochondrial function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.