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We demonstrate that tumor-intrinsic ceramide metabolism, amplified by dietary fat, initiates colorectal cancer metastasis. We observed that dietary fat exposure triggers a sustained increase in de novo ceramide biosynthesis, mediated by the dihydroceramide desaturase\n                    <jats:italic toggle=\"yes\">Degs1<\/jats:italic>\n                    . Ceramide accumulation activates yes-associated protein (YAP) through protein phosphatase 2A (PP2A)\u2013mediated dephosphorylation, promoting a durable shift toward a distinct YAP-driven regenerative (YAP-DR) program, marked by\n                    <jats:italic toggle=\"yes\">Basp1<\/jats:italic>\n                    , that promotes metastasis. Selective elimination of\n                    <jats:italic toggle=\"yes\">\n                      Basp1\n                      <jats:sup>high<\/jats:sup>\n                    <\/jats:italic>\n                    cancer cells prevented metastatic seeding.\n                    <jats:italic toggle=\"yes\">Degs1<\/jats:italic>\n                    loss reduced ceramide levels, YAP activity, YAP-DR signatures, and metastasis without affecting primary tumor growth, whereas blocking ceramide degradation enhanced YAP activity and metastasis. These findings identify ceramide-induced YAP signaling as a key mediator of metastatic initiation, operating independently of primary tumor expansion.\n                  <\/jats:p>","DOI":"10.1126\/science.adw8520","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:00:41Z","timestamp":1790272841000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Ceramide synthesis mediates colorectal cancer metastasis through a YAP-driven regenerative program"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-2860","authenticated-orcid":true,"given":"Swagata","family":"Goswami","sequence":"first","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Department of Molecular Pharmacology and Cancer Dormancy Institute, Albert Einstein College of Medicine, Bronx, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-2996","authenticated-orcid":true,"given":"Qiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Inflammation Department of Gilead Sciences, Foster City, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8921-2736","authenticated-orcid":true,"given":"Abdullah Burak","family":"Yildiz","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0775-0739","authenticated-orcid":true,"given":"Upasana","family":"Das Adhikari","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."},{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1628-5974","authenticated-orcid":true,"given":"Akhouri Kishore","family":"Raghawan","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2292-7046","authenticated-orcid":true,"given":"Manon","family":"Bulliard","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabhyata","family":"Sedhain","sequence":"additional","affiliation":[{"name":"David H. 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