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Restoring nuclear YAP activity reverses cisplatin resistance by impairing cisplatin-induced autophagy, shown by reduced LC3 puncta and Beclin-1 and increased p62. Autophagy inhibition with 3-methyladenine resensitizes resistant cells.",{"@graph":14,"@context":64},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/yap-inactivation-mediated-autophagy-inhibition-contributes-to-cisplatin-resistance-in-ovarian-cancer-cells/354334/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/yap-inactivation-mediated-autophagy-inhibition-contributes-to-cisplatin-resistance-in-ovarian-cancer-cells/354334.png","ImageObject",300,407,{"name":42,"@type":43},"Elsa","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":30},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58],{"name":59,"@type":60,"acceptedAnswer":61},"How is autophagy involved in the resistance mechanism?","Question",{"text":62,"@type":63},"YAP inactivation impairs cisplatin-induced autophagy. Resistant cells show blunted autophagic responses, with reduced LC3 puncta and Beclin-1 and increased p62; inhibiting autophagy with 3-methyladenine resensitizes cells to cisplatin.","Answer","https://schema.org",{"og:url":32,"og:type":66,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":68,"canonical":32},"index,follow",{"doc_id":70,"site_id":7},354334,1790126741,{"code":4,"msg":73,"data":74},"success",[75,79,83,87,92,97,102,106,111,114,118],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":76,"show_sort_weight":77,"slug":78},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":80,"show_sort_weight":81,"slug":82},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Exam",70,"exam",{"id":88,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},5,"Comic",60,"comic",{"id":93,"doc_module":4,"doc_module_name":25,"category_name":94,"show_sort_weight":95,"slug":96},6,"Technology",50,"technology",{"id":98,"doc_module":4,"doc_module_name":25,"category_name":99,"show_sort_weight":100,"slug":101},7,"Healthcare",40,"healthcare",{"id":103,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":104,"slug":105},8,30,"research-report",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},9,"Religion & Spirituality",20,"religion-spirituality",{"id":109,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":109,"slug":113},"World Cup","world-cup",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":115,"slug":117},10,"Lifestyle","lifestyle",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":88,"slug":121},19,"General","general",{"code":4,"msg":73,"data":123},{"doc_id":70,"user_id":124,"nickname":42,"user_avatar":125,"doc_module":4,"category_id":103,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":30,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":131,"language":132,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":133,"faqs":134,"seo_title":135,"seo_description":12,"update_tm":136,"read_time":137},137455077381,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Nguyen et al. Journal of Ovarian Research (2026) 19:221 Journal of Ovarian Research  \n[https://doi.org/10.1186/s13048-026-02127-5](https://doi.org/10.1186/s13048-026-02127-5)  \nRESEARCH Open Access  \nYAP inactivation-mediated autophagy inhibition contributes to cisplatin resistance in ovarian cancer cells  \nNgocThang Nguyen1†, Meng-Ru Hsieh 1†, Hieu Dac Hanh Nguyen 1, Waratchaya Chimphlee1, Sarinporn Visitsattapongse2 and Wen-Tai Chiu 1,3,4,5*  \nAbstract  \nBackground Cisplatin resistance remains a critical barrier in the treatment of high-grade serous ovarian cancer (HGSOC) . Although Hippo−YAP signaling regulates cancer progression, its contribution to cisplatin resistance is still poorly understood. Here, we demonstrate that YAP is inactivated and sequestered in the cytoplasm of cisplatinresistant ovarian cancer cells.  \nResults This cytosolic retention is mediated by Hippo kinases MST1/2 and LATS1/2, as well as ERK signaling, resulting in increased phosphorylation of YAP at its inhibitory site (Ser397) and reduced phosphorylation at its activating  \nsite (Tyr357) . Restoration of YAP activity through genetic overexpression or pharmacological induction of nuclear YAP accumulation significantly reversed cisplatin resistance. Mechanistically, YAP inactivation impaired cisplatininduced autophagy. Cisplatin robustly triggered autophagy in parental cells, as evidenced by LC3 puncta formation; however, this autophagic response was blunted in resistant cells. Overexpression of YAP further suppressed LC3 puncta formation and Beclin-1 expression, and increased p62 accumulation in cisplatin-resistant ovarian cancer cells. Autophagy inhibition using 3-methyladenine (3-MA) resensitized resistant cells to cisplatin.  \nConclusion Collectively, these findings reveal that YAP inactivation contributes to cisplatin resistance by abrogating autophagy formation and identify YAP reactivation as a potential strategy to overcome chemoresistance in ovarian cancer.  \nKeywords Ovarian cancer, Cisplatin resistance, YAP, Autophagy  \n†NgocThang Nguyen and Meng-Ru Hsieh contributed equally to this work.  \n*Correspondence:  \nWen-Tai Chiu  \n[wtchiu@mail.ncku.edu.tw](wtchiu@mail.ncku.edu.tw)  \n1Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan  \n2Department of Biomedical Engineering, School of Engineering, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand 3International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 701, Taiwan  \n4Medical Device Innovation Center, National Cheng Kung University, Tainan 701, Taiwan  \n5Center for Transformative Bioelectronic Medicine, National Cheng Kung University, Tainan 701, Taiwan  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.)  \nNguyen et al. Journal of Ovarian Research (2026) 19:221  \nIntroduction  \nHigh-grade serous ovarian cancer (HGSOC) is the ","cbCair0J7YpFfZNC","https://ap.wps.com/l/cbCair0J7YpFfZNC","pdf",7762096,13,"English","# Abstract\n## Background\n## Results\n## Mechanistic findings\n## Conclusion\n# Introduction\n## Clinical context of HGSOC and cisplatin resistance\n## Hippo pathway and YAP regulation\n## Upstream signaling influencing YAP/TAZ","[{\"question\":\"How is autophagy involved in the resistance mechanism?\",\"answer\":\"YAP inactivation impairs cisplatin-induced autophagy. Resistant cells show blunted autophagic responses, with reduced LC3 puncta and Beclin-1 and increased p62; inhibiting autophagy with 3-methyladenine resensitizes cells to cisplatin.\"}]","YAP inactivation-mediated autophagy inhibition contributes to cisplatin resistance in ovarian cancer cells | PDF",1790110164,33]