Analysis of DGAT Mutations Reveals Contributions to Cancer Progression
Start Date
29-4-2022 2:15 PM
Location
Alter Hall Poster Session 1 - 2nd floor
Abstract
Lipid metabolism is an essential cellular process, and alterations in lipid metabolism are characteristic of cancer cells. We hypothesized that disruptions in lipid regulatory genes such as the diacylglycerol acyltransferase enzymes (DGAT) 1 and 2, which code for triacylglycerol synthesis enzymes, are linked to carcinogenic metabolism. We analyzed DGAT1 and DGAT2 mutations in cancer samples from the Catalogue of Somatic Mutations in Cancers (COSMIC) database and found several pathogenic mutations including those that affect the catalytic site of the enzymes. Through statistical and bioinformatics analysis, we identified conserved pathogenic mutations that are likely to disrupt the structure of the DGAT enzymes and thus their enzymatic activity. To study the potential impact of loss of function mutations such as these, we examined Schizosaccharomyces pombe knockout mutants for dga1, the DGAT homolog in fission yeast. We found that disruption of dga1 resulted in deregulation of lipids under genotoxic conditions. Altogether, these results suggest that disruption of DGAT genes can lead to cellular deregulation of lipids in a manner that promotes cancer progression.
Analysis of DGAT Mutations Reveals Contributions to Cancer Progression
Alter Hall Poster Session 1 - 2nd floor
Lipid metabolism is an essential cellular process, and alterations in lipid metabolism are characteristic of cancer cells. We hypothesized that disruptions in lipid regulatory genes such as the diacylglycerol acyltransferase enzymes (DGAT) 1 and 2, which code for triacylglycerol synthesis enzymes, are linked to carcinogenic metabolism. We analyzed DGAT1 and DGAT2 mutations in cancer samples from the Catalogue of Somatic Mutations in Cancers (COSMIC) database and found several pathogenic mutations including those that affect the catalytic site of the enzymes. Through statistical and bioinformatics analysis, we identified conserved pathogenic mutations that are likely to disrupt the structure of the DGAT enzymes and thus their enzymatic activity. To study the potential impact of loss of function mutations such as these, we examined Schizosaccharomyces pombe knockout mutants for dga1, the DGAT homolog in fission yeast. We found that disruption of dga1 resulted in deregulation of lipids under genotoxic conditions. Altogether, these results suggest that disruption of DGAT genes can lead to cellular deregulation of lipids in a manner that promotes cancer progression.
