[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-375895-105":3,"doc-detail-375895-en":81,"detail-sidebar-cat-0-en-105":99},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","lipid-metabolic-reprogramming-drives-triglyceride-storage-and-variable-sensitivity-to-fasn-inhibition-in-endocrine-resistant-breast-cancer-cells","Lipid metabolic reprogramming drives triglyceride storage and variable sensitivity to FASN inhibition in endocrine-resistant breast cancer cells","","Research evaluates how lipid metabolic reprogramming contributes to endocrine resistance in ER-positive breast cancer and tests a clinically relevant FASN inhibitor. ER+ cell lines made resistant to Tamoxifen, Fulvestrant, or long-term estrogen withdrawal are profiled by global gene expression and lipidomics. Lipid storage is quantified by Oil Red O staining, while 13C2-acetate tracing assesses FASN activity and TVB-2640 efficacy, linking triglyceride accumulation, lipid droplet changes, and PUFA desaturation patterns to drug responses.",{"@graph":14,"@context":73},[15,34,56],{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/lipid-metabolic-reprogramming-drives-triglyceride-storage-and-variable-sensitivity-to-fasn-inhibition-in-endocrine-resistant-breast-cancer-cells/375895/",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/lipid-metabolic-reprogramming-drives-triglyceride-storage-and-variable-sensitivity-to-fasn-inhibition-in-endocrine-resistant-breast-cancer-cells/375895.png","ImageObject",300,407,{"name":42,"@type":43},"Maya Linwood","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What question does this study address about endocrine-resistant breast cancer cells?","Question",{"text":63,"@type":64},"It investigates how lipid metabolic reprogramming is altered in ER+ breast cancer cells with acquired endocrine resistance and whether these changes create sensitivity (or resistance) to a fatty acid synthase (FASN) inhibitor.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were endocrine-resistant cell models generated and compared?",{"text":68,"@type":64},"ER+ breast cancer cell lines resistant to Tamoxifen, Fulvestrant, or long-term estrogen withdrawal were derived, then compared with parental cells using global gene expression and lipidomic profiling.",{"name":70,"@type":61,"acceptedAnswer":71},"What is the main finding regarding TVB-2640 and lipid storage?",{"text":72,"@type":64},"TVB-2640 effectively reduces FASN activity and lipid storage in most conditions, associated with decreased triglyceride-related lipid accumulation, although lipid reduction did not consistently translate into reduced cell growth.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},375895,1790458398,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":86,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":87,"file_id":88,"file_url":89,"file_type":90,"file_size":91,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":92,"language":93,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":94,"faqs":95,"seo_title":96,"seo_description":12,"update_tm":97,"read_time":98},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d",7,"Ward et al. Breast Cancer Research (2025) 27:32 Breast Cancer Research  \n[https://doi.org/10.1186/s13058-025-01991-1](https://doi.org/10.1186/s13058-025-01991-1)  \nRESEARCH Open Access  \nLipid metabolic reprogramming drives triglyceride storage and variable sensitivity to FASN inhibition in endocrine-resistant breast cancer cells  \nAshley V. Ward 1, Duncan Riley 1, Kirsten E. Cosper 1, Jessica Finlay-Schultz 1, Heather M. Brechbuhl2, Andrew E. Libby3, Kaitlyn B. Hill4, Rohan R. Varshney4, Peter Kabos2, Michael C. Rudolph3† and Carol A. Sartorius 1*†  \nAbstract  \nBackground Lipid metabolic reprogramming is increasingly recognized as a hallmark of endocrine resistance in estrogen receptor-positive (ER+) breast cancer. In this study, we investigated alterations in lipid metabolism in  \nER + breast cancer cell lines with acquired resistance to common endocrine therapies and evaluated the efficacy of a clinically relevant fatty acid synthase (FASN) inhibitor.  \nMethods ER + breast cancer cell lines resistant to Tamoxifen (TamR), Fulvestrant (FulvR), and long-term estrogen withdrawal (EWD) were derived. Global gene expression and lipidomic profiling were performed to compare parental and endocrine resistant cells. Lipid storage was assessed using Oil Red O (ORO) staining. The FASN inhibitor TVB-2640 was tested for its impact on lipid storage and cell growth. 13C2-acetate tracing was used to evaluate FASN activity and the efficacy of TVB-2640 .  \nResults Endocrine resistant cells showed significant enrichment in lipid metabolism pathways and distinct lipidomic profiles, characterized by elevated triglyceride levels and enhanced cytoplasmic lipid droplets. 13C2-acetate tracing revealed increased FASN activity in endocrine resistant cells, which was effectively reduced by TVB-2640 . While TVB-2640 reduced lipid storage in most but not all cell lines, this did not correlate with decreased cell growth. Polyunsaturated fatty acids (PUFAs) containing 6 or more double bonds were elevated in endocrine resistant cells and remained unaffected or increased with TVB-2640 .  \nConclusion Endocrine resistant breast cancer cells undergo a metabolic shift toward increased triglyceride storage and PUFAs with high degrees of desaturation. While TVB-2640 reduced lipid storage in most conditions, it had limited effects on the growth of endocrine resistant breast cancer cells. Targeting specific lipid metabolic dependencies,  \n†Michael C. Rudolph and Carol A. Sartorius contributed equally to this work.  \n*Correspondence:  \nCarol A. Sartorius [Carol.Sartorius@cuanschutz.edu](Carol.Sartorius@cuanschutz.edu)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/.  \nWard et al. Breast Cancer Research (2025) 27:32 Page 2 of 15  \nparticularly pathways that produce PUFAs, represents a potential therapeutic strategy in endocrine resistant breast cancer.  \nKeywords Breast cancer, Endocrine resistance, lipid metabolism, Fatty acid, Lipidomics, Fatty acid synthase  \nBackground  \nOvercoming resistance to endocrine therapies represents a pivotal challenge for en","cbCaivoH2Qu0Zq9o","https://ap.wps.com/l/cbCaivoH2Qu0Zq9o","pdf",2712164,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Background (endocrine therapy resistance and lipid metabolism)\n## Role of lipogenesis in ER+ breast cancer","[{\"question\":\"What question does this study address about endocrine-resistant breast cancer cells?\",\"answer\":\"It investigates how lipid metabolic reprogramming is altered in ER+ breast cancer cells with acquired endocrine resistance and whether these changes create sensitivity (or resistance) to a fatty acid synthase (FASN) inhibitor.\"},{\"question\":\"How were endocrine-resistant cell models generated and compared?\",\"answer\":\"ER+ breast cancer cell lines resistant to Tamoxifen, Fulvestrant, or long-term estrogen withdrawal were derived, then compared with parental cells using global gene expression and lipidomic profiling.\"},{\"question\":\"What is the main finding regarding TVB-2640 and lipid storage?\",\"answer\":\"TVB-2640 effectively reduces FASN activity and lipid storage in most conditions, associated with decreased triglyceride-related lipid accumulation, although lipid reduction did not consistently translate into reduced cell growth.\"}]","Lipid metabolic reprogramming drives triglyceride storage and variable sensitivity to FASN inhibition in endocrine-resistant breast cancer cells | PDF",1790216545,38,{"code":4,"msg":82,"data":100},[101,105,109,113,118,123,126,131,136,139,142],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},"Exam",70,"exam",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},5,"Comic",60,"comic",{"id":119,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},6,"Technology",50,"technology",{"id":86,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":124,"slug":125},40,"healthcare",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":129,"slug":130},8,"Research & Report",30,"research-report",{"id":132,"doc_module":4,"doc_module_name":25,"category_name":133,"show_sort_weight":134,"slug":135},9,"Religion & Spirituality",20,"religion-spirituality",{"id":134,"doc_module":4,"doc_module_name":25,"category_name":137,"show_sort_weight":134,"slug":138},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":140,"show_sort_weight":55,"slug":141},"Lifestyle","lifestyle",{"id":143,"doc_module":4,"doc_module_name":25,"category_name":144,"show_sort_weight":114,"slug":145},19,"General","general"]