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Cholesterol-lowering was tested across breast and colorectal adenocarcinoma cell-line models using EMT inducers and cholesterol-modulatory compounds. HPβCD reduced free cholesterol, lipid rafts, and lipid droplets, reversed EMT-associated gene expression, and lowered invasion and multidrug resistance. The findings support cholesterol depletion as a potential therapeutic strategy to mitigate metastatic cancer progression.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cholesterol-lowering-treatment-blocks-epithelial-mesenchymal-transition-emt-associated-invasiveness-and-drug-resistance-in-breast-and-colorectal-adenocarcinoma-models/350512/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cholesterol-lowering-treatment-blocks-epithelial-mesenchymal-transition-emt-associated-invasiveness-and-drug-resistance-in-breast-and-colorectal-adenocarcinoma-models/350512.png","ImageObject",300,407,{"name":92,"@type":93},"Franzy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does EMT play in cancer progression and metastasis?","Question",{"text":112,"@type":113},"EMT is a cellular process that enables cancer cells to invade and metastasize. It involves loss of epithelial characteristics and gain of mesenchymal traits, supporting migratory and invasive behavior.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was cholesterol-lowering tested in relation to EMT?",{"text":117,"@type":113},"Cholesterol-lowering effects on EMT were evaluated using three cell line models and three EMT inducers. Compounds including MβCD, HPβCD, and simvastatin were used, with measurements of cholesterol-associated cellular components and EMT gene/protein expression.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the main outcomes of HPβCD treatment after EMT induction?",{"text":121,"@type":113},"Cholesterol depletion with HPβCD reversed EMT-associated expression patterns, reduced relative invasion in NMuMG cells, and lowered multidrug resistance measurements in MCF-7 cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},350512,1790148071,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Cancer Medicine  \n|  RESEARCH ARTICLE  OPEN ACCESS \u003Cbr>Cholesterol-Lowering Treatment Blocks\u003Cbr>Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models\u003Cbr>Shanen Perumal | Naaziyah Abdulla | Ruth Aronson | Mandeep Kaur \u003Cbr>School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa\u003Cbr>Correspondence: Mandeep Kaur ([mandeep.kaur@wits.ac.za](mandeep.kaur@wits.ac.za))\u003Cbr>Received: 4 August 2025 | Revised: 28 January 2026 | Accepted: 18 June 2026\u003Cbr>Keywords: cancer progression | cholesterol lowering | cyclodextrins | drug resistance | epithelial-mesenchymal transition |  |\n| --- | --- |\n| ABSTRACT\u003Cbr>Background: Epithelial-mesenchymal transition (EMT) is a cellular process involved in the invasion and metastasis of cancer cells. Deregulated cellular cholesterol is associated with treatment resistance and metastatic potential in cancer cells; however, the link between EMT and cholesterol is unclear.\u003Cbr>Methods: We tested the effect of cholesterol-lowering on EMT using three cell line models and three EMT inducers. EMT was induced in NMuMG, MCF-7 and HT-29 cells to assess the effect of cholesterol-modulatory compounds, MβCD, HPβCD and simvastatin. Free cholesterol, lipid droplets and lipid rafts in cellular membranes were evaluated using immunofluorescence microscopy. Expression of EMT-associated genes was assessed using immunofluorescent staining, RT-qPCR and Western blotting. Results: Following cholesterol depletion (free cholesterol, lipid rafts and lipid droplets) with HPβCD, RT-qPCR showed an increase in CDH1 expression (log2 fold change [log2FC] = 2.03; p \u003C 0.001), and a decrease in Vim (log2FC = −1.01; p \u003C 0.05) in NMuMG cells post EMT. Expression of cholesterol biosynthesis gene HMGCR (log2FC = −1.72; p\u003C 0.01), and efflux genes ABCA1 (log2FC = −1.74; p\u003C 0.01) and ABCG1 (log2FC = −4.81; p\u003C 0.001) were reduced. A 68.4%(p \u003C 0.001) reduction in relative invasion in NMuMG cells and a 41.3%(p \u003C 0.01) reduction in multidrug resistance measurements in MCF-7 cells were observed post-EMT after HPβCD treatment.\u003Cbr>Conclusion: Cholesterol depletion reversed EMT-associated expression patterns in all three cell models. Results from this study support cholesterol depletion as a potential therapeutic intervention for mitigating metastatic cancer progression. |  |\n| 1 | Introduction | occurs during embryonic development, wound healing and tissue regeneration. EMT can also drive cancer progression by |\n| Cancer is a leading cause of death worldwide, with rising inci- | enhancing the migratory and invasive properties of cells, en- |\n| dence and mortality rates that reflect the growth and ageing of | abling malignancy at distant organs [3] . Several different signal- |\n| the global population [1]. Metastasis accounts for approximately | ling pathways are involved in EMT-associated signalling, with |\n| 60.1% of cancer-related mortality, increasing to 66.7% when only | considerable cross-talk between signalling pathways, including |\n| considering solid tumours [2] . Epithelial-mesenchymal transi- | the TGFβ signal transduction pathway, hypoxia-induced sig- |\n| tion (EMT) is a reversible physiological process that normally | nalling with the concomitant expression of HIF-1α, and IL-6/ |\n| Shanen Perumal and Naaziyah Abdulla shared co-first Authors. |  |\n| This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.\u003Cbr>© 2026 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd. |  |\n\nCancer Medicine, 2026; 15:e72070 1 of 17  \n[https://doi.org/10.1002/cam4.72070](https://doi.org/10.1002/cam4.72070)  \nJAK2/STAT3 activation [4–6] . These signalling pathways upregulate the expression of EMT-inducing transcrip","cbCaimmdQI3Bq8AI","https://ap.wps.com/l/cbCaimmdQI3Bq8AI","pdf",8669731,17,"English","# Introduction\n# Abstract","[{\"question\":\"What role does EMT play in cancer progression and metastasis?\",\"answer\":\"EMT is a cellular process that enables cancer cells to invade and metastasize. It involves loss of epithelial characteristics and gain of mesenchymal traits, supporting migratory and invasive behavior.\"},{\"question\":\"How was cholesterol-lowering tested in relation to EMT?\",\"answer\":\"Cholesterol-lowering effects on EMT were evaluated using three cell line models and three EMT inducers. Compounds including MβCD, HPβCD, and simvastatin were used, with measurements of cholesterol-associated cellular components and EMT gene/protein expression.\"},{\"question\":\"What were the main outcomes of HPβCD treatment after EMT induction?\",\"answer\":\"Cholesterol depletion with HPβCD reversed EMT-associated expression patterns, reduced relative invasion in NMuMG cells, and lowered multidrug resistance measurements in MCF-7 cells.\"}]","Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models | PDF",1790089378,43]