ArticleCell death & disease2024
MAZ-mediated up-regulation of BCKDK reprograms glucose metabolism and promotes growth by regulating glucose-6-phosphate dehydrogenase stability in triple-negative breast cancer.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- The MAZ-POLD1 Signaling Axis Drives Cisplatin Resistance in Bladder Cancer by Activating DNA Damage Repair.Cancers · 2026Article
- Development and validation of an 11-CpG methylation signature-based nomogram for predicting prognosis in early-onset breast cancer.Translational cancer research · 2026Article
- MAZ-Mediated ubiquitin-conjugating enzyme E2C upregulation promotes breast cancer progression via the MAPK signaling pathway.Translational oncology · 2026Article
- Inhibition of RACGAP1 sensitizes triple-negative breast cancer cells to ferroptosis by regulating CPT1A-dependent fatty acid metabolism.Journal of experimental & clinical cancer research : CR · 2025Article
- Branched-Chain α Keto-Acid Dehydrogenase Kinase-Mediated AKT Phosphorylation Promotes RCC Tumorigenesis and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- The correlation between obesity and the occurrence and development of breast cancer.European journal of medical research · 2025Review
- Branched-Chain Amino Acid Metabolic Reprogramming and Cancer: Molecular Mechanisms, Immune Regulation, and Precision Targeting.Oncology research · 2025Review
- Targeting PGK1: A New Frontier in Breast Cancer Therapy Under Hypoxic Conditions.Current issues in molecular biology · 2024Review
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Authors and funding
19 authors.
Funding
Abstract
Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.
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