Enhanced triacylglycerol catabolism by carboxylesterase 1 promotes aggressive colorectal carcinoma

The ability to adapt low-nutrient microenvironments is essential for tumor cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-κB transcription factor pathway associates with advanced disease stages shorter patients CRC. has been shown drive tumor-promoting inflammation, cancer survival, intestinal epithelial (IEC) dedifferentiation mouse models of However, whether affects metabolic adaptations that fuel aggressive CRC unknown. Here, we identified carboxylesterase 1 (CES1) an NF-κB–regulated lipase linking obesity-associated inflammation fat metabolism adaptation energy stress CES1 promoted via cell-autonomous mechanisms fatty acid oxidation (FAO) prevent toxic build-up triacylglycerols. We found elevated expression correlated worse outcomes overweight Accordingly, drove consensus molecular subtype 4 (CMS4), which associated obesity, stemness, inflammation. was also upregulated gene amplifications its transcriptional regulator HNF4A CMS2 tumors, reinforcing clinical relevance a driver This subtype-based distribution unfavorable prognostic correlation distinguished from other intracellular triacylglycerol lipases suggest could provide route treat