ArticleInternational journal of cancer2015
Regulation of nonsmall-cell lung cancer stem cell like cells by neurotransmitters and opioid peptides.
Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Neural regulation of lung cancer: from mechanisms to clinical implications.European journal of medical research · 2025Review
- A multi-level exploration of the genetic basis between lung cancer and schizophrenia.Annals of general psychiatry · 2025Article
- Molecular mechanisms and clinical value of the correlation between depression and cancer.Medical oncology (Northwood, London, England) · 2025Review
- Stress regulatory hormones and cancer: the contribution of epinephrine and cancer therapeutic value of beta blockers.Endocrine · 2025Review
- The interplay between gut bacteria and targeted therapies: implications for future cancer treatments.Molecular medicine (Cambridge, Mass.) · 2025Review
- Decoding the metastatic nexus: how chronic stress reprograms neuroendocrine-metabolic-microbiome circuits to fuel tumor metastasis.American journal of cancer research · 2025Review
- Chronic stress promotes non-small cell lung cancer (NSCLC) progression through circMBOAT2 upregulation mediated by CTCF.Cancer gene therapy · 2024Article
- The multifaceted role of beta-blockers in overcoming cancer progression and drug resistance: Extending beyond cardiovascular disorders.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Pyrroline-5-carboxylate reductase 1 reprograms proline metabolism to drive breast cancer stemness under psychological stress.Cell death & disease · 2023Article
- Involvement of the Opioid Peptide Family in Cancer Progression.Biomedicines · 2023Review
- Chronic stress in solid tumor development: from mechanisms to interventions.Journal of biomedical science · 2023Review
- γ-aminobutyric acid alleviates LPS-induced acute lung injury in mice through upregulating type B receptors.Archives of medical science : AMS · 2023Article
- GABAMolecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
- Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors.Cell death discovery · 2022Article
- Chronic Stress Effects on Tumor: Pathway and Mechanism.Frontiers in oncology · 2021Review
- β-Adrenergic Signaling in Lung Cancer: A Potential Role for Beta-Blockers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Effect of β-Blocker in Treatment-Naïve Patients With Advanced Lung Adenocarcinoma Receiving First-Generation EGFR-TKIs.Frontiers in oncology · 2020Article
- The Neuro-Psychological Axis of Smoking-Associated Cancer.Journal of immunological sciences · 2019Article
- Repurposing established cyclic adenosine monophosphate reducing agents for the prevention and therapy of epidermal growth factor receptor inhibitor resistance in non-small cell lung cancer.Translational lung cancer research · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nonsmall-cell lung cancer (NSCLC) is the leading type of lung cancer and has a poor prognosis. We have shown that chronic stress promoted NSCLC xenografts in mice via stress neurotransmitter-activated cAMP signaling downstream of beta-adrenergic receptors and incidental beta-blocker therapy was reported to improve clinical outcomes in NSCLC patients. These findings suggest that psychological stress promotes NSCLC whereas pharmacologically or psychologically induced decreases in cAMP may inhibit NSCLC. Cancer stem cells are thought to drive the development, progression and resistance to therapy of NSCLC. However, their potential regulation by stress neurotransmitters has not been investigated. In the current study, epinephrine increased the number of cancer stem cell like cells (CSCs) from three NSCLC cell lines in spheroid formation assays while enhancing intracellular cAMP and the stem cell markers sonic hedgehog (SHH), aldehyde dehydrogenase-1 (ALDH-1) and Gli1, effects reversed by GABA or dynorphin B via Gαi -mediated inhibition of cAMP formation. The growth of NSCLC xenografts in a mouse model of stress reduction was significantly reduced as compared with mice maintained under standard conditions. Stress reduction reduced serum levels of corticosterone, norepinephrine and epinephrine while the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and opioid peptides increased. Stress reduction significantly reduced cAMP, VEGF, p-ERK, p-AKT, p-CREB, p-SRc, SHH, ALDH-1 and Gli1 in xenograft tissues whereas cleaved caspase-3 and p53 were induced. We conclude that stress neurotransmitters activate CSCs in NSCLC via multiple cAMP-mediated pathways and that pharmacologically or psychologically induced decreases in cAMP signaling may improve clinical outcomes in NSCLC patients.
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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.