{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T16:42:16Z","timestamp":1792341736604,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20784"],"award-info":[{"award-number":["U24A20784"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473812"],"award-info":[{"award-number":["82473812"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82607360"],"award-info":[{"award-number":["82607360"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024MD764002"],"award-info":[{"award-number":["2024MD764002"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Oxaliplatin (L\u2010OHP) is a first\u2010line chemotherapeutic agent for advanced colorectal cancer (CRC) and postoperative adjuvant therapy. However, acquired L\u2010OHP resistance remains a clinical obstacle. Here, we identify Tubocapsenolide A (TA), a natural withanolide isolated from\n                    <jats:italic>Tubocapsicum anomalum<\/jats:italic>\n                    , as a promising antitumor agent that suppresses CRC growth and sensitizes L\u2010OHP\u2010resistant CRC to L\u2010OHP. Using a PROTAC\u2010based target deconvolution strategy, we identify PLK1 as a direct molecular target of TA. PLK1 is elevated in L\u2010OHP\u2010resistant CRC and is associated with reduced patient sensitivity to L\u2010OHP. Mechanistically, elevated PLK1 promotes CEP55 Ser436 phosphorylation and facilitates ESCRT recruitment to nuclear and mitochondrial budding sites. This process facilitates the clearance of L\u2010OHP\u2010induced damaged components through nuclear budding and TOM20\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/PDH\n                    <jats:sup>+<\/jats:sup>\n                    mitochondrial\u2010derived vesicles, thereby contributing to organelle homeostasis and cell survival. By inhibiting PLK1, TA interferes with this vesicle\u2010associated damage clearance process, leading to intracellular accumulation of damaged components. This damage accumulation is accompanied by nucleolar stress and mitochondrial dysfunction, ultimately contributing to cell death. Collectively, our findings identify a previously unappreciated role of the PLK1\u2013CEP55\u2013ESCRT axis in vesicle\u2010associated damage clearance during L\u2010OHP resistance and support this axis as a potential therapeutic target. TA represents a promising lead compound for overcoming L\u2010OHP resistance in CRC.\n                  <\/jats:p>","DOI":"10.1002\/advs.78310","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T16:10:57Z","timestamp":1792339857000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tubocapsenolide A Overcomes Oxaliplatin Resistance in Colorectal Cancer by Targeting PLK1 to Impair CEP55\u2013ESCRT\u2010Associated Vesicular Damage Clearance"],"prefix":"10.1002","author":[{"given":"Yueying","family":"Yang","sequence":"first","affiliation":[{"name":"Wuya College of Innovation Shenyang Pharmaceutical University Shenyang People's Republic of China"},{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liang","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation Shenyang Pharmaceutical University Shenyang People's Republic of China"},{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4084-6331","authenticated-orcid":false,"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M Nanjing Hospital of Chinese Medicine Nanjing University of Chinese Medicine Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Tissue Engineering and Regenerative Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiruo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation Shenyang Pharmaceutical University Shenyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation Shenyang Pharmaceutical University Shenyang People's Republic of China"},{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation Shenyang Pharmaceutical University Shenyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-8029","authenticated-orcid":false,"given":"Wen","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-801X","authenticated-orcid":false,"given":"Dejuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation Shenyang Pharmaceutical University Shenyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xiang","sequence":"additional","affiliation":[{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Digital Materia Medica and Structural Pharmacology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy Fujian University of Traditional Chinese Medicine Fuzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-869X","authenticated-orcid":false,"given":"Zhimin","family":"Fan","sequence":"additional","affiliation":[{"name":"Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M Nanjing Hospital of Chinese Medicine Nanjing University of Chinese Medicine Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-0728","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of 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