Forcing ATGL expression in hepatocarcinoma cells imposes glycolytic rewiring through PPAR-α/p300-mediated acetylation of p53.

ABSTRACT: Metabolic reprogramming is a typical feature of cancer cells aimed at sustaining high-energetic demand and proliferation rate. Here, we report clear-cut evidence for decreased expression of the adipose triglyceride lipase (ATGL), the first and rate-limiting enzyme of triglyceride hydrolysis, in both human and mouse-induced hepatocellular carcinoma (HCC). We identified metabolic rewiring as major outcome of ATGL overexpression in HCC-derived cell lines. Indeed, ATGL slackened both glucose uptake/utilization and cell proliferation in parallel with increased oxidative metabolism of fatty acids and enhanced mitochondria capacity. We ascribed these ATGL-downstream events to the activity of the tumor-suppressor p53, whose protein levels-but not transcript-were upregulated upon ATGL overexpressio

SUBMITTER: Di Leo L 

PROVIDER: S-EPMC6756110 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature