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Updated: Jul 2, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug
Shanen Perumal1, Naaziyah Abdulla1, Ruth Aronson1
1School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.
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 (log2 fold change [log2FC] = 2.03; p < 0.001), and a decrease in Vim (log2FC = -1.01; p < 0.05) in NMuMG cells post EMT. Expression of cholesterol biosynthesis gene HMGCR (log2FC = -1.72; p < 0.01), and efflux genes ABCA1 (log2FC = -1.74; p < 0.01) and ABCG1 (log2FC = -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.
Insights
Cholesterol depletion reversed cancer cell changes associated with metastasis and drug resistance. This suggests lowering cholesterol could be a new strategy to fight cancer progression.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Epithelial-mesenchymal transition (EMT) drives cancer cell invasion and metastasis.
- Altered cholesterol metabolism is linked to cancer treatment resistance and metastasis.
- The relationship between EMT and cellular cholesterol levels remains unclear.
Purpose of the Study:
- To investigate the effect of cholesterol-lowering interventions on EMT.
- To determine if modulating cholesterol impacts cancer cell metastatic potential and drug resistance.
Main Methods:
- Utilized three cancer cell lines (NMuMG, MCF-7, HT-29) and three EMT inducers.
- Administered cholesterol-modulating compounds (MβCD, HPβCD, simvastatin).
- Assessed changes in free cholesterol, lipid droplets, lipid rafts, and EMT-associated gene expression via immunofluorescence, RT-qPCR, and Western blotting.
Main Results:
- Cholesterol depletion using HPβCD reversed EMT markers, increasing CDH1 and decreasing Vim expression in NMuMG cells.
- Reduced expression of cholesterol biosynthesis (HMGCR) and efflux (ABCA1, ABCG1) genes was observed.
- Significant reductions in NMuMG cell invasion (68.4%) and MCF-7 cell multidrug resistance (41.3%) were noted post-treatment.
Conclusions:
- Cholesterol depletion effectively reversed EMT-associated molecular alterations across multiple cell models.
- These findings highlight cholesterol depletion as a promising therapeutic approach to combat metastatic cancer progression and enhance treatment efficacy.
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