# Ezetimibe inhibits the migration and invasion of triple‐negative breast cancer cells by targeting TGFβ2 and EMT

**Authors:** Lingkai Kong, Qinyu He, Ding Ma, Weiwei Shi, Qilei Xin, Chunping Jiang, Junhua Wu

PMC · DOI: 10.1002/2211-5463.13797 · FEBS Open Bio · 2024-03-26

## TL;DR

Ezetimibe may help treat triple-negative breast cancer by blocking cell migration and invasion through TGFβ2 and EMT, independent of cholesterol uptake.

## Contribution

Ezetimibe's anti-metastatic effect is shown to be independent of cholesterol inhibition, targeting TGFβ2 and EMT in triple-negative breast cancer.

## Key findings

- Ezetimibe inhibits breast cancer cell migration, invasion, and EMT.
- Ezetimibe significantly suppresses TGFβ2 expression in breast cancer cells.
- Overexpression of TGFβ2 reverses the anti-metastatic effects of ezetimibe.

## Abstract

The important role of cholesterol in tumor metastasis has been widely studied in recent years. Ezetimibe is currently the only selective cholesterol uptake inhibitor on the market. Here, we explored the effect of ezetimibe on breast cancer metastasis by studying its impact on breast cancer cell migration, invasion, and epithelial‐mesenchymal transition (EMT). Differential gene expression analysis and validation were also carried out to compare ezetimibe‐treated and untreated breast cancer cells. Finally, breast cancer cells overexpressing TGFβ2 were constructed, and the effect of TGFβ2 on the migration and invasion of ezetimibe‐treated breast cancer cells was examined. Our results show that ezetimibe treatment of breast cancer cells inhibited cell migration, invasion, and EMT, and it significantly suppressed the expression of TGFβ2. Overexpression of TGFβ2 reversed the inhibitory effect of ezetimibe on the migration and invasion of breast cancer cells. Taken together, our results suggest that ezetimibe might be a potential candidate for the treatment of breast cancer metastasis.

The important role of cholesterol in tumor metastasis has been widely studied recently. Ezetimibe, the only selective cholesterol uptake inhibitor on the market, inhibits the migration and invasion of triple‐negative breast cancer cells by targeting TGFβ2 and EMT without relying on inhibiting cholesterol uptake. Overall, our findings suggest a unique mechanism by which ezetimibe prevents breast cancer metastasis.

## Linked entities

- **Genes:** TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042]
- **Chemicals:** ezetimibe (PubChem CID 150311)
- **Diseases:** triple-negative breast cancer (MONDO:0005494)

## Full-text entities

- **Genes:** TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042] {aka CAEND2, G-TSF, LDS4, TGF-beta2}
- **Diseases:** breast cancer (MESH:D001943), tumor metastasis (MESH:D009362), triple-negative breast cancer (MESH:D064726)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11073500/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC11073500/full.md

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Source: https://tomesphere.com/paper/PMC11073500