Lipid Metabolism in Cancer: The Role of Acylglycerolphosphate Acyltransferases (AGPATs)

Altered lipid metabolism is an emerging hallmark of aggressive tumors, as rapidly proliferating cancer cells reprogram fatty acid (FA) uptake, synthesis, storage, and usage to meet their increased energy demands. Central to these adaptive changes, is the conversion of excess FA to neutral triacylgly...

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Bibliographic Details
Published in:Cancers 2022-01, Vol.14 (1), p.228
Main Authors: Karagiota, Angeliki, Chachami, Georgia, Paraskeva, Efrosyni
Format: Article
Language:English
Subjects:
Adipocytes
Amino acids
Apoptosis
Biosynthesis
Breast cancer
Cancer
Cell proliferation
Cell signaling
Chemoresistance
Enzymes
Fatty acids
Genes
Glycerol
Isoforms
Lipid metabolism
Lipids
Lipodystrophy
Liver
Localization
Lysophosphatidic acid
Medical prognosis
Membranes
Metabolism
Mitochondria
Mutation
Phenotypes
Phosphatidic acid
Phospholipids
Proteins
Review
Sterols
Substrate specificity
Tumors
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Summary:Altered lipid metabolism is an emerging hallmark of aggressive tumors, as rapidly proliferating cancer cells reprogram fatty acid (FA) uptake, synthesis, storage, and usage to meet their increased energy demands. Central to these adaptive changes, is the conversion of excess FA to neutral triacylglycerides (TAG) and their storage in lipid droplets (LDs). Acylglycerolphosphate acyltransferases (AGPATs), also known as lysophosphatidic acid acyltransferases (LPAATs), are a family of five enzymes that catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), the second step of the TAG biosynthesis pathway. PA, apart from its role as an intermediate in TAG synthesis, is also a precursor of glycerophospholipids and a cell signaling molecule. Although the different AGPAT isoforms catalyze the same reaction, they appear to have unique non-overlapping roles possibly determined by their distinct tissue expression and substrate specificity. This is best exemplified by the role of AGPAT2 in the development of type 1 congenital generalized lipodystrophy (CGL) and is also manifested by recent studies highlighting the involvement of AGPATs in the physiology and pathology of various tissues and organs. Importantly, AGPAT isoform expression has been shown to enhance proliferation and chemoresistance of cancer cells and correlates with increased risk of tumor development or aggressive phenotypes of several types of tumors.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14010228