{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:29:30Z","timestamp":1786418970585,"version":"build-2736575974"},"reference-count":92,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["118720"],"award-info":[{"award-number":["118720"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epithelial\u2010mesenchymal 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested the effect of cholesterol\u2010lowering on EMT using three cell line models and three EMT inducers. EMT was induced in NMuMG, MCF\u20107 and HT\u201029 cells to assess the effect of cholesterol\u2010modulatory compounds, M\u03b2CD, HP\u03b2CD and simvastatin. Free cholesterol, lipid droplets and lipid rafts in cellular membranes were evaluated using immunofluorescence microscopy. Expression of EMT\u2010associated genes was assessed using immunofluorescent staining, RT\u2010qPCR and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following cholesterol depletion (free cholesterol, lipid rafts and lipid droplets) with HP\u03b2CD, RT\u2010qPCR showed an increase in\n                      <jats:italic>CDH1<\/jats:italic>\n                      expression (log\n                      <jats:sub>2<\/jats:sub>\n                      fold change [log\n                      <jats:sub>2<\/jats:sub>\n                      FC]\u2009=\u20092.03;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and a decrease in\n                      <jats:italic>Vim<\/jats:italic>\n                      (log\n                      <jats:sub>2<\/jats:sub>\n                      FC\u2009=\u2009\u22121.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in NMuMG cells post EMT. Expression of cholesterol biosynthesis gene\n                      <jats:italic>HMGCR<\/jats:italic>\n                      (log\n                      <jats:sub>2<\/jats:sub>\n                      FC\u2009=\u2009\u22121.72;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and efflux genes\n                      <jats:italic>ABCA1<\/jats:italic>\n                      (log\n                      <jats:sub>2<\/jats:sub>\n                      FC\u2009=\u2009\u22121.74;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and\n                      <jats:italic>ABCG1<\/jats:italic>\n                      (log\n                      <jats:sub>2<\/jats:sub>\n                      FC\u2009=\u2009\u22124.81;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) were reduced. A 68.4% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) reduction in relative invasion in NMuMG cells and a 41.3% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) reduction in multidrug resistance measurements in MCF\u20107 cells were observed post\u2010EMT after HP\u03b2CD treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cholesterol depletion reversed EMT\u2010associated expression patterns in all three cell models. Results from this study support cholesterol depletion as a potential therapeutic intervention for mitigating metastatic cancer progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72070","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:53:27Z","timestamp":1782921207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cholesterol\u2010Lowering Treatment Blocks Epithelial\u2010Mesenchymal Transition (\n                    <scp>EMT<\/scp>\n                    ) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models"],"prefix":"10.1002","volume":"15","author":[{"given":"Shanen","family":"Perumal","sequence":"first","affiliation":[{"name":"School of Molecular and Cell Biology University of the Witwatersrand  Johannesburg South 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