# DNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis

**Authors:** Qianqian Cao, Gongwen Xu, Guanghui Huang, Sheng Li, Hao Li, Xiaonan Zhang, Xiaomei Li

PMC · DOI: 10.1038/s41419-025-08167-x · Cell Death & Disease · 2025-12-11

## TL;DR

This study shows that DNMT1 increases RASSF1A methylation, promoting breast cancer spread to the brain, suggesting DNMT1 as a potential treatment target.

## Contribution

The study identifies DNMT1 as a key driver of RASSF1A methylation in breast cancer brain metastasis.

## Key findings

- DNMT1 promotes tumor cell viability, migration, and invasion in breast cancer.
- RASSF1A is a direct target of DNMT1-mediated methylation.
- DNMT1-driven RASSF1A methylation facilitates brain metastasis in breast cancer.

## Abstract

Epigenetic modifications, particularly DNA methylation, play a critical role in the metastatic progression of breast cancer. This study investigates the role of DNA methyltransferase 1 (DNMT1) in regulating the methylation of RASSF1A and its contribution to breast cancer brain metastasis. Using single-cell transcriptome sequencing of CTCs derived from in situ breast cancer models, DNMT1 was identified as a key promoter of tumor cell viability, migration, and invasion. RASSF1A was further validated as a direct target of DNMT1-mediated methylation. This regulatory interaction was confirmed through DNA methylation sequencing, methylation-specific PCR, and chromatin immunoprecipitation assays. These findings highlight the pivotal role of DNMT1-driven RASSF1A methylation in facilitating breast cancer metastasis to the brain, and suggest that targeting DNMT1 may represent a promising therapeutic approach for managing metastatic breast cancer.

## Linked entities

- **Genes:** DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786], RASSF1 (Ras association domain family member 1) [NCBI Gene 11186]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, RASSF1 (Ras association domain family member 1) [NCBI Gene 11186] {aka 123F2, NORE2A, RASSF1A, RDA32, REH3P21}
- **Diseases:** metastasis (MESH:D009362), tumor (MESH:D009369), breast cancer (MESH:D001943)

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12830775/full.md

## References

7 references — full list in the complete paper: https://tomesphere.com/paper/PMC12830775/full.md

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Source: https://tomesphere.com/paper/PMC12830775