ArticleThe Journal of clinical investigation2019
Stress-induced epinephrine enhances lactate dehydrogenase A and promotes breast cancer stem-like cells.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
169 citing papers in PubMed, 1 synthesis or guideline pooled it, 309 citations in OpenAlex.
- Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients.Molecular psychiatry · 2020Pooled it
- Postoperative effect of sufentanil preemptive analgesia combined with psychological intervention on breast cancer patients.BMC anesthesiology · 2023Trial
- Psychological stress and tumor progression: Molecular mechanisms and therapeutic implications (Review).Oncology letters · 2026Review
- RBM25 Drives Hepatocellular Carcinoma Progression by Stabilizing YAP Through Regulating Oncogenic Splicing-switch of MYPT1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Amuc_1473 Links Gut Microbes to Skeletal Homeostasis and Counteracts Multifactorial Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Depression remodels tumor microenvironment to drive tumor progression: Bio-behavioural signalling pathways and clinical interventions.Journal of advanced research · 2026Review
- Sympathetic immunomodulation suppresses liver metastasis by maintaining the balance between norepinephrine concentration and the α2a/β2-AR ratio.Cellular & molecular immunology · 2026Article
- Epicatechin Gallate Blocks GC/GR Signaling to Suppress Stress-Induced Myeloid Differentiation of HSPCs and Subsequent TNBC Metastasis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.BMC medicine · 2026Review
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- LDHA-Mediated H3K18 Lactylation Promotes the Glycolysis in Non-Small Cell Lung Cancer Through Targeting PTEN.Biochemical genetics · 2026Article
- Lactate metabolism and lactylation: Therapeutic and pre-clinical implications in neovascularization in peripheral artery disease.Journal of pharmaceutical analysis · 2026Review
- Tyrosine hydroxylase as a therapeutic target: insights from adrenergic nerve and TNBC cell interactions.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Associations of genetic polymorphisms with boldness, stress response, and route efficiency in homing pigeons (Columba livia).Physiology & behavior · 2026Article
- The therapeutic effects of labetalol in chronic stress- and immuno-agonist-induced cough hypersensitivity and lung inflammation involve reducing interferon-γ-producing T lymphocytes.ERJ open research · 2026Article
- Pretreatment emotional distress and peripheral biomarkers predict immune checkpoint inhibitor response in people with advanced inoperable gastroesophageal cancer.Communications medicine · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
109 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 10 institutions in 3 countries.
Funding
Abstract
Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress-induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A-dependent (LDHA-dependent) metabolic rewiring. Chronic stress-induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress-induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer.
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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.