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. 2022 Jan 27;9(1):2024051.
doi: 10.1080/23723556.2021.2024051. eCollection 2022.

Rewired lipid metabolism as an actionable vulnerability of aggressive colorectal carcinoma

Daria Capece  1   2 , Guido Franzoso  1
Affiliations

Rewired lipid metabolism as an actionable vulnerability of aggressive colorectal carcinoma

Daria Capece et al. Mol Cell Oncol. .

Abstract

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.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Carboxylesterase (CES)1-dependent metabolic rewiring in colorectal carcinoma (CRC) etiopathogenesis. CES1 is upregulated by HNF4A and NF-κB in the Consensus Molecular Subtype (CMS)2 and CMS4 CRC subtypes and promotes tumor cell survival by increasing triacylglycerol (TAG) breakdown to fuel fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) during starvation and preventing toxic lipid accumulation, which triggers apoptosis and ferroptosis. as CES1 is also expressed in adipocytes, we speculate it may also play a role in the symbiosis of CRC cells with adipocytes.
See this image and copyright information in PMC

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