ArticleProceedings of the National Academy of Sciences of the United States of America2015
Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 219 citations in OpenAlex.
- Local production of lactate, ribose phosphate, and amino acids within human triple-negative breast cancer.Med (New York, N.Y.) · 2021Trial
- Weak supervision of H&E slides reveals systems-level biology and functional states that govern therapeutic resistance.bioRxiv : the preprint server for biology · 2026Article
- Decoding drug-responsive cell subpopulations in triple-negative breast cancer using single-cell multiomics.iScience · 2026Article
- Glucose metabolic reprogramming: a novel strategy to enhance radiotherapy response to triple-negative breast cancer.Frontiers in public health · 2026Review
- TXNIP upregulation controls metabolism and cell cycle during androgen deprivation therapy in prostate cancer.Cell death & disease · 2025Article
- Metabolic interplay between exogenous cystine and glutamine dependence in triple-negative breast cancer.Cell death discovery · 2025Article
- Metabolomics as a tool for understanding and treating triple-negative breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Mitochondria-Associated Pathways in Cancer and Precancerous Conditions: Mechanistic Insights.International journal of molecular sciences · 2025Review
- Adipocytes-induced ANGPTL4/KLF4 axis drives glycolysis and metastasis in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.Cell communication and signaling : CCS · 2025Article
- Molecular mechanisms underlying TXNIP's anti-tumor role in breast cancer, including interaction with a novel, pro-tumor partner: CAST.Cell death & disease · 2025Article
- Nidogen-1 suppresses cell proliferation, migration, and glycolysis via integrin β1-mediated HIF-1α downregulation in triple-negative breast cancer.Scientific reports · 2025Article
- Molecular heterogeneity and MYC dysregulation in triple-negative breast cancer: genomic advances and therapeutic implications.3 Biotech · 2025Review
- Molecular Effects of Glucose onBritish journal of biomedical science · 2025Article
- Transmembrane Amino Acid Transporters in Shaping the Metabolic Profile of Breast Cancer Cell Lines: The Focus on Molecular Biological Subtype.Current issues in molecular biology · 2024Review
- Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation.Lipids in health and disease · 2024Article
- Identification and Experimental Validation of Prognostic miRNA Signature and Ferroptosis-Related Key Genes in Cervical Squamous Cell Carcinoma.Cancer medicine · 2024Article
- Article
- The activation of the G-protein-coupled estrogen receptor promotes the aggressiveness of MDA-MB231 cells by targeting the IRE1α/TXNIP pathway.Research in pharmaceutical sciences · 2024Article
- Oncogenic Control of Metabolism.Cold Spring Harbor perspectives in medicine · 2024Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancers (TNBCs) are aggressive and lack targeted therapies. Understanding how nutrients are used in TNBCs may provide new targets for therapeutic intervention. We demonstrate that the transcription factor c-Myc drives glucose metabolism in TNBC cells but does so by a previously unappreciated mechanism that involves direct repression of thioredoxin-interacting protein (TXNIP). TXNIP is a potent negative regulator of glucose uptake, aerobic glycolysis, and glycolytic gene expression; thus its repression by c-Myc provides an alternate route to c-Myc-driven glucose metabolism. c-Myc reduces TXNIP gene expression by binding to an E-box-containing region in the TXNIP promoter, possibly competing with the related transcription factor MondoA. TXNIP suppression increases glucose uptake and drives a dependence on glycolysis. Ectopic TXNIP expression decreases glucose uptake, reduces cell proliferation, and increases apoptosis. Supporting the biological significance of the reciprocal relationship between c-Myc and TXNIP, a Mychigh/TXNIPlow gene signature correlates with decreased overall survival and decreased metastasis-free survival in breast cancer. The correlation between the Mychigh/TXNIPlow gene signature and poor clinical outcome is evident only in TNBC, not in other breast cancer subclasses. Mutation of TP53, which is a defining molecular feature of TNBC, enhances the correlation between the Mychigh/TXNIPlow gene signature and death from breast cancer. Because Myc drives nutrient utilization and TXNIP restricts glucose availability, we propose that the Mychigh/TXNIPlow gene signature coordinates nutrient utilization with nutrient availability. Further, our data suggest that loss of the p53 tumor suppressor cooperates with Mychigh/TXNIPlow-driven metabolic dysregulation to drive the aggressive clinical behavior of TNBC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.