ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Adrenergic Stimulation of DUSP1 Impairs Chemotherapy Response in Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 91 citations in OpenAlex.
- Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1).British journal of cancer · 2024Trial
- Chronic psychological stress and gastric cancer: bidirectional associations, biological mechanisms, and clinical implications-a narrative review.Journal of gastrointestinal oncology · 2026Review
- Stress‑induced catecholamines attenuate sorafenib efficacy by inhibiting ferroptosis in β2‑adrenergic receptor positive renal cell carcinoma.International journal of oncology · 2026Article
- The DAG/PKC/CREB1/TGF-β1 axis drives shear-wave elastography stiffness and malignant progression in triple-negative breast cancer via lipid metabolic reprogramming.Cell death & disease · 2026Article
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- Review
- The neuro-immune axis in cancer: from mechanisms to therapeutic opportunities.Journal of hematology & oncology · 2025Review
- Neurotransmitters: an emerging target for therapeutic resistance to tumor immune checkpoint inhibitors.Molecular cancer · 2025Review
- Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells.Cancer research and treatment · 2025Article
- Impact of Tumoral β2-Adrenergic Receptor Expression on Chemotherapeutic Response and Prognosis in Patients with Advanced Colorectal Cancer.Annals of surgical oncology · 2025Article
- Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.MedComm · 2024Review
- Fallopian Tube-Derived High-Grade Serous Cancers Influence Ovarian Production of Norepinephrine and Generate Specific Metabolomic Signatures.ACS pharmacology & translational science · 2024Article
- Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Review
- Norepinephrine induces anoikis resistance in high-grade serous ovarian cancer precursor cells.JCI insight · 2024Article
- Deciphering the tumor immune microenvironment of imatinib-resistance in advanced gastrointestinal stromal tumors at single-cell resolution.Cell death & disease · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- The sympathetic nervous system shapes the tumor microenvironment to impair chemotherapy response.Frontiers in oncology · 2024Review
- Pathogenesis and therapeutic strategies for cancer-related depression.American journal of cancer research · 2024Review
- Chronic Stress Blocks the Endometriosis Immune Response by Metabolic Reprogramming.International journal of molecular sciences · 2023Article
- Multiple types of distress are prospectively associated with increased risk of ovarian cancer.Cancer medicine · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeChronic adrenergic activation has been shown to associate with adverse clinical outcomes in cancer patients, but the underlying mechanisms are not well understood. The focus of the current study was to determine the functional and biologic effects of adrenergic pathways on response to chemotherapy in the context of ovarian cancer. EXPERIMENTAL
designIncreased DUSP1 production by sympathetic nervous system mediators (e.g., norepinephrine) was analyzed by real-time quantitative RT-PCR and by Western blotting. In vitro chemotherapy-induced cell apoptosis was examined by flow cytometry. For in vivo therapy, a well-characterized model of chronic stress was used.
resultsCatecholamines significantly inhibited paclitaxel- and cisplatin-induced apoptosis in ovarian cancer cells. Genomic analyses of cells treated with norepinephrine identified DUSP1 as a potential mediator. DUSP1 overexpression resulted in reduced paclitaxel-induced apoptosis in ovarian cancer cells compared with control; conversely, DUSP1 gene silencing resulted in increased apoptosis compared with control cells. DUSP1 gene silencing in vivo significantly enhanced response to paclitaxel and increased apoptosis. In vitro analyses indicated that norepinephrine-induced DUSP1 gene expression was mediated through ADRB2 activation of cAMP-PLC-PKC-CREB signaling, which inhibits JNK-mediated phosphorylation of c-Jun and protects ovarian cancer cells from apoptosis. Moreover, analysis of The Cancer Genome Atlas data showed that increased DUSP1 expression was associated with decreased overall (P= 0.049) and progression-free (P= 0.0005) survival.
conclusionsThese findings provide a new understanding of the mechanisms by which adrenergic pathways can impair response to chemotherapy and have implications for cancer management.
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