{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:55:07Z","timestamp":1790085307540,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Nationale contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ligue Interr\u00e9gionale contre le Cancer"},{"name":"Ligue contre le Cancer Comit\u00e9 de C\u00f4te d\u2019Or"},{"DOI":"10.13039\/100007380","name":"Fondation de l\u2019Avenir","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007380","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"crossref","award":["ANR-11-LABX-0021"],"award-info":[{"award-number":["ANR-11-LABX-0021"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chemoresistance remains a major barrier to effective colorectal cancer (CRC) therapy, yet its metabolic underpinnings are poorly defined. Here, we integrate lipidomic profiling, enzymatic analysis, and functional perturbation approaches to elucidate the contribution of phosphatidylcholine (PC) metabolism and its biosynthetic regulator Choline Phosphotransferase 1 (CHPT1) to drug response. Comparative analysis of chemosensitive and chemoresistant CRC cell lines revealed that resistant HT29 cells exhibited significantly higher PC content and altered PC\/lysophosphatidylcholine (LPC)ratios relative to sensitive counterparts. Importantly, functional perturbation confirmed causality: CHPT1 overexpression in SW620 cells was sufficient to promote PC accumulation and confer a chemoresistant phenotype. These findings identify CHPT1 as a metabolic gatekeeper of chemoresistance. Consistently, Human Protein Atlas survival analyses further support its clinical relevance, as elevated CHPT1 expression correlates with poor patient outcomes in CRC. Mechanistically, CHPT1-driven PC enrichment may sustain pro-survival signaling, while reducing lysophospholipid-mediated stress pathways. To therapeutically target this vulnerability, we investigated edelfosine (Edel), an alkyl-lysophospholipid that disrupts lipid rafts and inhibits PC biosynthesis upstream of CHPT1. Notably, edelfosine-mediated disruption of the Kennedy pathway enhances chemosensitivity in the resistant CRC model. Collectively, our study identifies CHPT1 and PC metabolism as central determinants of CRC drug response and proposes edelfosine-based metabolic reprogramming as a promising strategy to overcome resistance.<\/jats:p>","DOI":"10.3390\/cells15050439","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phosphatidylcholine and CHPT1 as Central Drivers of Chemoresistance in Colorectal Cancer: Lipidomic and Functional Insights"],"prefix":"10.3390","volume":"15","author":[{"given":"Aur\u00e9lie","family":"Mialhe","sequence":"first","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, INSERM, CTM UMR 1231, TIRECS Team, Bioactive Molecules and Health Research Group, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Pais de Barros","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, Centre de Lutte Contre le Cancer G.-F. Leclerc, Institut Agro, CHU Dijon Bourgogne, INSERM, BioSanD US 58 (Diviomics Platform), 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-1992","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Hermetet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, INSERM, CTM UMR 1231, TIRECS Team, Bioactive Molecules and Health Research Group, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeric","family":"Limagne","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, Centre de Lutte Contre le Cancer G.-F. Leclerc, INSERM, CTM UMR 1231, TIRECS Team, 21000 Dijon, France"},{"name":"Universit\u00e9 Bourgogne Europe, Centre de Lutte Contre le Cancer G.-F. Leclerc, Institut Agro, CHU Dijon Bourgogne, INSERM, BioSanD US 58 (PTBC Platform), 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5465-8305","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Ghiringhelli","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, Centre de Lutte Contre le Cancer G.-F. Leclerc, INSERM, CTM UMR 1231, TIRECS Team, 21000 Dijon, France"},{"name":"Universit\u00e9 Bourgogne Europe, Centre de Lutte Contre le Cancer G.-F. Leclerc, Institut Agro, CHU Dijon Bourgogne, INSERM, BioSanD US 58 (PTBC Platform), 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9331-5014","authenticated-orcid":false,"given":"Virginie","family":"Aires","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, INSERM, CTM UMR 1231, TIRECS Team, Bioactive Molecules and Health Research Group, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8911-8499","authenticated-orcid":false,"given":"Dominique","family":"Delmas","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Bourgogne Europe, INSERM, CTM UMR 1231, TIRECS Team, Bioactive Molecules and Health Research Group, 21000 Dijon, France"},{"name":"Universit\u00e9 Bourgogne Europe, Centre de Lutte Contre le Cancer G.-F. Leclerc, INSERM, CTM UMR 1231, TIRECS Team, Bioactive Molecules and Health Research Group, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118095","DOI":"10.1016\/j.biopha.2025.118095","article-title":"Lipid metabolism in cancer: Exploring phospholipids as potential biomarkers","volume":"187","author":"Delmas","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","first-page":"45","article-title":"Reprogrammed lipid metabolism in advanced resistant cancers: An upcoming therapeutic opportunity","volume":"7","author":"Cioce","year":"2024","journal-title":"Cancer Drug. Resist."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1039\/C9MO00128J","article-title":"Lipid mechanisms in hallmarks of cancer","volume":"16","author":"Molendijk","year":"2020","journal-title":"Mol. 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