{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T09:25:56Z","timestamp":1782033956573,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81874111"],"award-info":[{"award-number":["No. 81874111"]}],"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":["No. 81972482"],"award-info":[{"award-number":["No. 81972482"]}],"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":["No. 82372649"],"award-info":[{"award-number":["No. 82372649"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018617","name":"Liaoning Revitalization Talents Program","doi-asserted-by":"publisher","award":["XLYC2002043"],"award-info":[{"award-number":["XLYC2002043"]}],"id":[{"id":"10.13039\/501100018617","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Platinum\u2010based therapies have revolutionized the treatment of high\u2010grade serous ovarian cancer (HGSOC). However, high rates of disease recurrence and progression remain a major clinical concern. Impaired mitochondrial function and dysregulated reactive oxygen species (ROS), hallmarks of cancer, hold potential as therapeutic targets for selectively sensitizing cisplatin treatment. Here, we uncover an oncogenic role of the palmitoyltransferase ZDHHC12 in regulating mitochondrial function and ROS homeostasis in HGSOC cells. Analysis of The Cancer Genome Atlas (TCGA) ovarian cancer data revealed significantly elevated <jats:italic>ZDHHC12<\/jats:italic> expression, demonstrating the strongest positive association with ROS pathways among all ZDHHC enzymes. Transcriptomic analysis of independent ovarian cancer datasets and the SNU119 cell model corroborated this association, highlighting a strong link between <jats:italic>ZDHHC12<\/jats:italic> expression and signature pathways involving mitochondrial oxidative metabolism and ROS regulation. Knockdown of <jats:italic>ZDHHC12<\/jats:italic> disrupted this association, leading to increased cellular complexity, ATP levels, mitochondrial activity, and both mitochondrial and cellular ROS. This dysregulation, achieved by the siRNA knockdown of <jats:italic>ZDHHC12<\/jats:italic> or treatment with the general palmitoylation inhibitor 2BP or the fatty acid synthase inhibitor C75, significantly enhanced cisplatin cytotoxicity in 2D and 3D spheroid models of HGSOC through ROS\u2010mediated mechanisms. Markedly, ZDHHC12 inhibition significantly augmented the anti\u2010tumor activity of cisplatin in an ovarian cancer xenograft tumor model, as well as in an ascites\u2010derived organoid line of platinum\u2010resistant ovarian cancer. Our data suggest the potential of ZDHHC12 as a promising target to improve the outcome of HGSOCs in response to platinum\u2010based chemotherapy.<\/jats:p>","DOI":"10.1111\/cas.16085","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T07:55:10Z","timestamp":1706601310000},"page":"1170-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of palmitoyltransferase <scp>ZDHHC12<\/scp> sensitizes ovarian cancer cells to cisplatin through <scp>ROS<\/scp>\u2010mediated mechanisms"],"prefix":"10.1111","volume":"115","author":[{"given":"Xining","family":"Zhang","sequence":"first","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingming","family":"Liao","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Han","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"An","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiezheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5618-8709","authenticated-orcid":false,"given":"Hailing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pixu","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Institute, Dalian Key Laboratory of Molecular Targeted Cancer Therapy, The Second Hospital of Dalian Medical University Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21456"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32552-2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.05.019"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102925"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1691"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114205"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2084"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846666"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20160304"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.073954"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15781"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.04.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1139"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26180-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4002"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26082382"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.07.025"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2081-4"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.384"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005637"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1507"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151089"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.03.027"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.12.024"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.812264"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.116.033514"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2512"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.734897"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0375-6"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3987"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2021.07.002"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.06.020"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708313"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3126"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02159-4"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1536"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022019056"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-520"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.03.008"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.16085","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T04:19:07Z","timestamp":1712809147000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.16085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/cas.16085"],"URL":"https:\/\/doi.org\/10.1111\/cas.16085","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,29]]},"assertion":[{"value":"2023-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}