Posttranslational control of lipogenesis in the tumor microenvironment

Abstract

Metabolic reprogramming of cancer cells within the tumor microenvironment typically occurs in response to increased nutritional, translation and proliferative demands. Altered lipid metabolism is a marker of tumor progression that is frequently observed in aggressive tumors with poor prognosis. Underlying these abnormal metabolic behaviors are posttranslational modifications (PTMs) of lipid metabolism-related enzymes and other factors that can impact their activity and/or subcellular localization. This review focuses on the roles of these PTMs and specifically on how they permit the re-wiring of cancer lipid metabolism, particularly within the context of the tumor microenvironment.

Keywords: Cancer; Lipid metabolism reprogramming; Posttranslational modification; Tumor microenvironment.

Fig. 1

Signaling pathways of lipid metabolism in cancer. The magenta box indicates up-regulation of the respective enzyme and the green box indicates down-regulation

Fig. 2

The phosphorylation-mediated control of lipid metabolism enzymes during tumorigenesis. The red boxes represent protein kinases, which mediate the phosphorylation of these lipid-metabolizing enzymes, and the yellow boxes represent phosphatases, which are responsible for de-phosphorylation of lipid metabolism enzymes during tumorigenesis

Fig. 3

Acetylation-mediated control of lipid metabolism enzymes during tumorigenesis. Red boxes represent acetylation transferase, which mediates the acetylation of lipid metabolism enzymes. Yellow boxes indicate deacetylases, which remove the acetylation modification of lipid metabolism enzymes during cancer development

Fig. 4

Ubiquitination-mediated control of lipid metabolism enzymes in tumorigenesis. The red box represents ubiquitinases, which regulate the ubiquitination of lipid metabolism enzymes. Yellow boxes indicate de-ubiquitinating enzymes

Fig. 5

Cross talk between different PTMs in cancer lipid metabolism. Domains are drawn to scale. S, Serine; K, lysine; P, phosphorylation; Ub, ubiquitination; Ac, acetylation; ME1, malic enzyme 1; ACLY, ATP citrate lyase; SREBP1, sterol regulatory element-binding protein 1; GNPAT, glyceronephosphate O-acyltransferase; LPLATs, lysophospholipid acyltransferases; DP acyltransferase, dihydroxyacetone phosphate acyltransferase; BLLF1, Herpes virus major outer envelope glycoprotein; and bHLHzip, basic helix–loop–helix–zipper domain