Dysregulated metabolism is an emerging hallmark of
cancer development, and upregulated
lipid synthesis is one of the important
tumor metabolic features. However, lipolysis may also contribute to
cancer pathogenesis by altering
free fatty acid (FFA) metabolism. In the present study, we investigated the importance of the lipolytic
enzyme acyl-CoA thioesterase 8 (ACOT8) in
hepatocellular carcinoma (HCC) development. Bioinformatic analysis of published microarrays regarding clinical specimens revealed that both ACOT8 gene copy number and
mRNA expression were increased in HCC tissues when compared to these variables in non-
tumor tissues. ACOT8 silencing with specific
shRNA stably expressed in Huh7 and Hep3B HCC cell lines showed that ACOT8
protein expression and overall thioesterase activity were reduced following ACOT8 knockdown. In vitro tumorigenic assays revealed that ACOT8 knockdown inhibited anchorage-dependent and ‑independent growth of HCC cell lines. This growth inhibition was partially rescued by addition of the FFA,
myristic acid, indicating the importance of FFA in
cancer metabolism. In summary, lipolytic
enzyme ACOT8 is frequently upregulated in HCC clinical specimens. More importantly, ACOT8 silencing leads to inhibition of cell growth in HCC in vitro.