Rewired lipid metabolism as an actionable vulnerability of aggressive colorectal carcinoma.

Cancer cells reprogram lipid metabolism to fuel cell division, adaptation to stress, and metastatic dissemination. NF-κB transcription factors control this mechanism in aggressive Consensus Molecular Subtype (CMS)4 of colorectal carcinoma (CRC) via triacylglycerol (TAG) lipase, carboxylesterase 1 (CES1), thereby linking obesity-associated inflammation with metabolic adaptation and cytoprotection from lipid-induced toxicity. Our findings identify a potential therapeutic route to treat patients with metastasis-prone CRC and provide an example for targeting core tumor subtype-based vulnerabilities in cancers beyond CRC.