ArticleScience advances2025
FAM50A drives breast cancer brain metastasis through interaction with C9ORF78 to enhance ʟ-asparagine production.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Article
- Complex I protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases.Nature communications · 2026Article
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance.Frontiers in cell and developmental biology · 2026Article
- Inhibition of apoptosis in breast cancer cells by si-FoxO3a through the protein digestion and absorption signaling pathway.Oncology letters · 2025Article
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Authors and funding
16 authors.
Funding
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Abstract
Elevated levels of asparagine, catalyzed by asparagine synthetase (ASNS), have been identified as a prerequisite for lung metastasis in breast cancer. However, the roles and regulatory mechanisms of ASNS in breast cancer brain metastasis (BCBM) are not well understood. Our study revealed that the family with sequence similarity 50 member A (FAM50A) gene substantially modulates the brain metastatic potential of breast cancer by up-regulating ASNS and promoting asparagine biosynthesis. We demonstrated that FAM50A forms a complex with chromosome 9 open reading frame 78 (C9ORF78), specifically at the S121 residue, to enhance ASNS transcription. This interaction accelerates the rate of ASNS-mediated asparagine synthesis, which is essential in facilitating metastatic cascades to the brain. From a therapeutic perspective, both the genetic suppression of FAM50A and pharmacological inhibition of asparagine synthesis effectively counteract BCBM. Our results highlight the importance of the FAM50A-ASNS signaling pathway in BCBM therapy.
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