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Updated: Jan 8, 2026

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DNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis
Qianqian Cao1, Gongwen Xu2, Guanghui Huang3
1Cancer Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, PR China.
None:
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.
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