ArticleMetabolomics : Official journal of the Metabolomic Society2022
Metabolite profiling reveals a connection between aldehyde dehydrogenase 1A3 and GABA metabolism in breast cancer metastasis.
Article in Metabolomics : Official journal of the Metabolomic Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Molecular and Clinicopathological Biomarkers Predicting Brain Metastasis in Triple-Negative Breast Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells.Nature cancer · 2026Article
- Single-cell landscape of intratumoral heterogeneity and GABA-mediated remodeling of the immune microenvironment in breast cancer metastases.Breast cancer research : BCR · 2026Article
- Selective inhibition of ALDH1A3 impedes breast cancer growth and metastasis by blocking ALDH1A3-driven transcriptional programs.iScience · 2026Article
- Gamma-aminobutyric acid affects the tumor microenvironment and angiogenesis, promoting breast cancer progression.CytoJournal · 2026Article
- Neuroendocrine carcinoma of the cervix (NECC): A retrospective study of 175 Chinese patients.European journal of obstetrics & gynecology and reproductive biology: X · 2025Article
- SLC45A4 encodes a peroxisomal putrescine transporter that promotes GABA de novo synthesis.Nature communications · 2025Article
- Circulating levels of glutamate predict brain disease in patients with advanced lung and breast cancer: a prospective study.Journal of neuro-oncology · 2025Observational
- Distinctive GABA A receptor subunit expression modulates cell specific EMT and functional responses in glioblastoma breast and ovarian cancer.Scientific reports · 2025Article
- Tumor cells upregulate neurotransmitter GABA in the choroid plexus through STAT6-Bestrophin1 signaling, promoting leptomeningeal dissemination.Neuro-oncology · 2025Article
- Neurotransmitter power plays: the synaptic communication nexus shaping brain cancer.Acta neuropathologica communications · 2025Review
- The double role of GABAergic system in systemic tumors: an updated review.Frontiers in oncology · 2025Review
- PdJournal of medicinal chemistry · 2024Article
- Recent advances in the biosynthesis and industrial biotechnology of Gamma-amino butyric acid.Bioresources and bioprocessing · 2024Review
- ALDH1A3 promotes invasion and metastasis in triple-negative breast cancer by regulating the plasminogen activation pathway.Molecular oncology · 2024Article
- The tumor-nerve circuit in breast cancer.Cancer metastasis reviews · 2023Review
- Review
- Identification of Novel Prognostic Biomarkers That are Associated with Immune Microenvironment Based on GABA-Related Molecular Subtypes in Gastric Cancer.Pharmacogenomics and personalized medicine · 2023Article
- Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
introductionAldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell (CSC) marker and in breast cancer it is associated with triple-negative/basal-like subtypes and aggressive disease. Studies on the mechanisms of ALDH1A3 in cancer have primarily focused on gene expression changes induced by the enzyme; however, its effects on metabolism have thus far been unstudied and may reveal novel mechanisms of pathogenesis.
objectiveDetermine how ALDH1A3 alters the metabolite profile in breast cancer cells and assess potential impacts.
methodTriple-negative MDA-MB-231 tumors and cells with manipulated ALDH1A3 levels were assessed by HPLC-MS metabolomics and metabolite data was integrated with transcriptome data. Mice harboring MDA-MB-231 tumors with or without altered ALDH1A3 expression were treated with γ-aminobutyric acid (GABA) or placebo. Effects on tumor growth, and lungs and brain metastasis were quantified by staining of fixed thin sections and quantitative PCR. Breast cancer patient datasets from TCGA, METABRIC and GEO were used to assess the co-expression of GABA pathway genes with ALDH1A3.
resultsIntegrated metabolomic and transcriptome data identified GABA metabolism as a primary dysregulated pathway in ALDH1A3 expressing breast tumors. Both ALDH1A3 and GABA treatment enhanced metastasis. Patient dataset analyses revealed expression association between ALDH1A3 and GABA pathway genes and corresponding increased risk of metastasis.
conclusionThis study revealed a novel pathway affected by ALDH1A3, GABA metabolism. Like ALDH1A3 expression, GABA treatment promotes metastasis. Given the clinical use of GABA mimics to relieve chemotherapy-induced peripheral nerve pain, further study of the effects of GABA in breast cancer progression is warranted.
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Registered trials
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