ArticleJournal of experimental & clinical cancer research : CR2023
Chronic stress accelerates glioblastoma progression via DRD2/ERK/β-catenin axis and Dopamine/ERK/TH positive feedback loop.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 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
- Chronic stress drives gastric cancer lymph node metastasis via NETosis through a feedforward ACh-NGF axis-mediated PKC-γ/STAT3 pathway.Oncogene · 2026Article
- Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.Cell communication and signaling : CCS · 2026Review
- From Antipsychotic to Antitumor Agent: Cariprazine Suppresses Glioblastoma via D2/D3-ARRB2 Axis Modulation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- PPP1R18-mediated activation of Wnt/β-catenin and EMT is dependent on ERK signaling in clear cell renal cell carcinoma.Cancer cell international · 2026Article
- A comparative investigation of catecholamines and glucocorticoids impact on glioblastoma invasive behavior via 2D and 3D cell culture.PloS one · 2026Article
- Neurotransmitter-Mediated Signaling in Glioblastoma and Glial Tumors: Biology and Therapeutic Opportunities.Oncology research · 2026Review
- The role of the tumor microenvironment in mediating radiopharmaceutical therapy: bridging nuclear medicine and cancer immunotherapy.Military Medical Research · 2026Review
- Effective Synthesis of Dopamine Dimer.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Article
- Multimorbidity and animal models.Animal models and experimental medicine · 2025Review
- Advances in the study of the relationship between neurotransmitters and gastric cancer.World journal of gastroenterology · 2025Review
- Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.Biomarker research · 2025Review
- Neurotransmitter Regulatory Networks: A New Perspective on Cancer Therapy.Biomolecules · 2025Review
- Review
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Prevalence and Independent Risk Factors of Anxiety and Depression Symptoms in Glioma Patients: A Cross-Sectional Analysis.Psychiatry and clinical psychopharmacology · 2025Article
- Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders.Medical gas research · 2025Review
- Amino acid metabolism in glioblastoma pathogenesis, immune evasion, and treatment resistance.Cancer cell international · 2025Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAfter diagnosis, glioblastoma (GBM) patients undertake tremendous psychological problems such as anxiety and depression, which may contribute to GBM progression. However, systematic study about the relationship between depression and GBM progression is still lacking.
methodsChronic unpredictable mild stress and chronic restrain stress were used to mimic human depression in mice. Human GBM cells and intracranial GBM model were used to assess the effects of chronic stress on GBM growth. Targeted neurotransmitter sequencing, RNA-seq, immunoblotting and immunohistochemistry were used to detect the related molecular mechanism.
resultsChronic stress promoted GBM progression and up-regulated the level of dopamine (DA) and its receptor type 2 (DRD2) in tumor tissues. Down-regulation or inhibition of DRD2 abolished the promoting effect of chronic stress on GBM progression. Mechanistically, the elevated DA and DRD2 activated ERK1/2 and consequently inhibited GSK3β activity, leading to β-catenin activation. Meanwhile, the activated ERK1/2 up-regulated tyrosine hydroxylase (TH) level in GBM cells and then promoted DA secretion, forming an autocrine positive feedback loop. Remarkably, patients with high-depression exhibited high DRD2 and β-catenin levels, which showed poor prognosis. Additionally, DRD2 specific inhibitor pimozide combined with temozolomide synergistically inhibited GBM growth.
conclusionsOur study revealed that chronic stress accelerates GBM progression via DRD2/ERK/β-catenin axis and Dopamine/ERK/TH positive feedback loop. DRD2 together with β-catenin may serve as a potential predictive biomarker for worse prognosis as well as therapeutic target of GBM patients with depression.
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Registered trials
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