{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:58:26Z","timestamp":1785473906393,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102024\u201000344706"],"award-info":[{"award-number":["RS\u20102024\u201000344706"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Peroxisome proliferator\u2010activated receptor gamma (PPAR\u03b3), a well\u2010characterized regulator of adipogenesis, also functions as a tumor suppressor in breast cancer. However, the PPAR\u03b3 agonist rosiglitazone has shown limited clinical efficacy, highlighting the importance of understanding PPAR\u03b3 regulation within the tumor microenvironment. Here, we demonstrate that adipocyte\u2010derived palmitic acid promotes PPAR\u03b3 S\u2010palmitoylation via zinc finger DHHC\u2010domain containing protein 15 (ZDHHC15), as confirmed by acyl\u2010biotin exchange (ABE) assay. Immunoblot, RT\u2010qPCR, and immunoprecipitation further revealed that this modification leads to ubiquitin\u2010mediated proteasomal degradation of PPAR\u03b3. Functional studies using adipocyte\u2010conditioned media and an oxygen\u2010permeable 3D spheroid culture system showed that PPAR\u03b3 palmitoylation promotes breast cancer malignancy and confers resistance to rosiglitazone. Notably, the palmitoylation inhibitor 2\u2010bromopalmitate (2\u2010BP) stabilizes PPAR\u03b3, suppressing breast cancer malignancy. Furthermore, 2\u2010BP synergistically enhances the therapeutic efficacy of rosiglitazone, suggesting that targeting PPAR\u03b3 S\u2010palmitoylation represents a promising therapeutic strategy in breast cancer.<\/jats:p>","DOI":"10.1111\/cas.70487","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:12:49Z","timestamp":1785471169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipocyte\u2010Derived Palmitic Acid Promotes Breast Cancer Malignancy via\n                    <scp>ZDHHC15<\/scp>\n                    \u2010Mediated S\u2010Palmitoylation of\n                    <scp>PPAR\u03b3<\/scp>"],"prefix":"10.1111","author":[{"given":"Geon Ho","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Physiology Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Physiology Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Pathology Seoul National University Hospital  Seoul Republic of Korea"},{"name":"Cancer Research Institute, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Yong","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Seoul National University Hospital  Seoul Republic of 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