Cancer Med. 2026 Jul;15(7):e72070. doi: 10.1002/cam4.72070.
ABSTRACT
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.
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 (log fold change [logFC] = 2.03; p < 0.001), and a decrease in Vim (logFC = -1.01; p < 0.05) in NMuMG cells post EMT. Expression of cholesterol biosynthesis gene HMGCR (logFC = -1.72; p < 0.01), and efflux genes ABCA1 (logFC = -1.74; p < 0.01) and ABCG1 (logFC = -4.81; p < 0.001) were reduced. A 68.4% (p < 0.001) reduction in relative invasion in NMuMG cells and a 41.3% (p < 0.01) reduction in multidrug resistance measurements in MCF-7 cells were observed post-EMT after HPβCD treatment.
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.
PMID:42383765 | DOI:10.1002/cam4.72070