ArticleMolecular oncology2019
Preventing BRCA1/ZBRK1 repressor complex binding to the GOT2 promoter results in accelerated aspartate biosynthesis and promotion of cell proliferation.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Oxaloacetate inhibition of succinate dehydrogenase: mechanism and physiological implications.American journal of physiology. Cell physiology · 2026Review
- Research Progress on the Physiological Functions of Aspartic Acid and Its Applications in Animal Production.Animals : an open access journal from MDPI · 2026Review
- Integrated analysis of glutamine metabolism and immune microenvironment identifies GOT2 as a prognostic gene in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- Comprehensive Experimental and Computational Characterization of a Phenylacetamide-Based Molecule.BioMed research international · 2026Article
- Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.Frontiers in oncology · 2026Article
- Comprehensive investigation of the molecular basis of cancer dependencies suggests therapeutic options for breast cancer.Cancer biology & medicine · 2025Article
- Article
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- Glucose-induced STUB1-GOT2 axis promotes aspartate synthesis and mitochondrial dysfunction in bladder cancer.Cell death & disease · 2025Article
- GOT2: New therapeutic target in pancreatic cancer.Genes & diseases · 2025Review
- Construction of molecular subtypes and prognostic model for breast cancer based on sulfur metabolism-related genes.Translational cancer research · 2025Article
- Mitochondrial glutamic-oxaloacetic transaminase (GOT2) in the growth of C2C12 myoblasts.Journal of bioenergetics and biomembranes · 2025Article
- GOT2: a moonlighting enzyme at the crossroads of cancer metabolism and theranostics.Frontiers in immunology · 2025Review
- Isotoosendanin inhibits triple-negative breast cancer metastasis by reducing mitochondrial fission and lamellipodia formation regulated by the Smad2/3-GOT2-MYH9 signaling axis.Acta pharmacologica Sinica · 2024Article
- Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence.Human genomics · 2024Article
- HECW1 induces NCOA4-regulated ferroptosis in glioma through the ubiquitination and degradation of ZNF350.Cell death & disease · 2023Article
- BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.International journal of molecular sciences · 2023Review
- Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer.International journal of molecular sciences · 2023Review
- BMI-1 promotes breast cancer proliferation and metastasis through different mechanisms in different subtypes.Cancer science · 2023Article
- PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Breast cancer susceptibility gene 1 (BRCA1) has been implicated in modulating metabolism via transcriptional regulation. However, direct metabolic targets of BRCA1 and the underlying regulatory mechanisms are still unknown. Here, we identified several metabolic genes, including the gene which encodes glutamate-oxaloacetate transaminase 2 (GOT2), a key enzyme for aspartate biosynthesis, which are repressed by BRCA1. We report that BRCA1 forms a co-repressor complex with ZBRK1 that coordinately represses GOT2 expression via a ZBRK1 recognition element in the promoter of GOT2. Impairment of this complex results in upregulation of GOT2, which in turn increases aspartate and alpha ketoglutarate production, leading to rapid cell proliferation of breast cancer cells. Importantly, we found that GOT2 can serve as an independent prognostic factor for overall survival and disease-free survival of patients with breast cancer, especially triple-negative breast cancer. Interestingly, we also demonstrated that GOT2 overexpression sensitized breast cancer cells to methotrexate, suggesting a promising precision therapeutic strategy for breast cancer treatment. In summary, our findings reveal that BRCA1 modulates aspartate biosynthesis through transcriptional repression of GOT2, and provides a biological basis for treatment choices in breast cancer.
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Registered trials
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