ArticleCancer research2021
Psychologic Stress Drives Progression of Malignant Tumors via DRD2/HIF1α Signaling.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Psychological stress and tumor progression: Molecular mechanisms and therapeutic implications (Review).Oncology letters · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Dopamine inhibits retinal pathological neovascularization in the oxygen-induced retinopathy mouse model.The Journal of pathology · 2026Article
- Anticancer Effects of Fluphenazine Alone and in Combination with Cisplatin in Gastric Cancer Cells and a Mouse Xenograft Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.Neoplasia (New York, N.Y.) · 2026Review
- Review
- Chemoproteomic profiling reveals histone H4 dopaminylation inhibiting cell growth.Nature chemical biology · 2026Article
- Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.International journal of molecular sciences · 2026Review
- Pharmacologic targeting of the dopamine D2 receptor impacts the efficacy of immune checkpoint blockade in melanoma.Journal for immunotherapy of cancer · 2026Article
- The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Chronic stress-related neuroendocrine mediators and ovarian cancer.Discover oncology · 2025Review
- Research progress on chronic stress stimulation and gastric cancer metastasis.Discover oncology · 2025Review
- Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.Biomarker research · 2025Review
- Neurotransmitter Regulatory Networks: A New Perspective on Cancer Therapy.Biomolecules · 2025Review
- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- Shared and Unique Genetic Links between Neuroticism and Gastrointestinal Tract Diseases.Depression and anxiety · 2024Article
- The combined signatures of G protein-coupled receptor family and immune landscape provide a prognostic and therapeutic biomarker in endometrial carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Dopamine receptors gene overexpression in the microenvironment of invasive gastric cancer and its potential implications.Molecular biology reports · 2023Article
- A Holistic Approach to Hard-to-Treat Cancers: The Future of Immunotherapy for Glioblastoma, Triple Negative Breast Cancer, and Advanced Prostate Cancer.Biomedicines · 2023Review
- Chronic stress accelerates glioblastoma progression via DRD2/ERK/β-catenin axis and Dopamine/ERK/TH positive feedback loop.Journal of experimental & clinical cancer research : CR · 2023Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although it is established that the sustained psychologic stress conditions under which patients with tumors often reside accelerates malignant progression of tumors, the molecular mechanism behind this association is unclear. In this work, the effect of psychologic stress on tumor progression was verified using a stress-stimulated tumor-bearing mouse model (Str-tumor). Both D2 dopamine receptor (DRD2) and hypoxia-inducible factor-1α (HIF1α) were highly expressed in the nucleus of Str-tumors. Treatment with trifluoperazine (TFP), a DRD2 inhibitor, elicited better antitumor effects in Str-tumors than the control group. These results indicate that DRD2 may mediate stress-induced malignant tumor progression. DRD2 interacted with von Hippel-Lindau (VHL) in the nucleus, and competitive binding of DRD2 and HIF1α to VHL resulted in reduced ubiquitination-mediated degradation of HIF1α, enhancing the epithelial-mesenchymal transition of tumor cells. TFP acted as an interface inhibitor between DRD2 and VHL to promote the degradation of HIF1α. In conclusion, DRD2 may promote the progression of malignant tumors induced by psychologic stress via activation of the oxygen-independent HIF1α pathway, and TFP may serve as a therapeutic strategy for stress management in patients with cancer. SIGNIFICANCE: This work identifies DRD2 regulation of HIF1α as a mechanism underlying the progression of malignant tumors stimulated by psychologic stress and suggests that DRD2 inhibition can mitigate these stress conditions in patients.
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