ArticleEuropean journal of cancer (Oxford, England : 1990)2016
Nicotine induces self-renewal of pancreatic cancer stem cells via neurotransmitter-driven activation of sonic hedgehog signalling.
Article in European journal of cancer (Oxford, England : 1990), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Network toxicology and interpretable modeling identify nicotine-associated neuroendocrine targets and a three-gene prognostic signature in breast cancer.Translational cancer research · 2026Article
- Review
- Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities.Molecular cancer · 2025Review
- Cholinergic Mechanisms in Gastrointestinal Neoplasia.International journal of molecular sciences · 2024Review
- Cell signaling and epigenetic regulation of nicotine-induced carcinogenesis.Environmental pollution (Barking, Essex : 1987) · 2024Review
- Effect of Nicotine on Immune System Function.Advanced pharmaceutical bulletin · 2023Review
- Article
- Multiple roles for cholinergic signaling in pancreatic diseases.World journal of gastroenterology · 2022Review
- GABAMolecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer.Frontiers in genetics · 2022Article
- The connection between innervation and metabolic rearrangements in pancreatic cancer through serine.Frontiers in oncology · 2022Review
- Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management.Cancers · 2020Review
- The dual role of alpha7 nicotinic acetylcholine receptor in inflammation-associated gastrointestinal cancers.Heliyon · 2020Review
- Cigarette smoke supports stemness and epithelial-mesenchymal transition in bladder cancer stem cells through SHH signaling.International journal of clinical and experimental pathology · 2020Article
- Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness.Cancers · 2019Review
- Observational
- The Neuro-Psychological Axis of Smoking-Associated Cancer.Journal of immunological sciences · 2019Article
- Article
- Regulation of Sox2 and stemness by nicotine and electronic-cigarettes in non-small cell lung cancer.Molecular cancer · 2018Article
- Hedgehog Signaling in Lung Cancer: From Oncogenesis to Cancer Treatment Resistance.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A small subpopulation of pancreatic cancer cells with characteristics of stem cells drive tumour initiation, progression and metastasis. A better understanding of the regulation of cancer stem cells may lead to more effective cancer prevention and therapy. We have shown that the proliferation and migration of pancreatic cancer cell lines is activated by the nicotinic receptor-mediated release of stress neurotransmitters, responses reversed by γ-aminobutyric acid (GABA). However, the observed cancer inhibiting effects of GABA will only succeed clinically if GABA inhibits pancreatic cancer stem cells (PCSCs) in addition to the more differentiated cancer cells that comprise the majority of cancer tissues and cell lines. Using PCSCs isolated from two pancreatic cancer patients by cell sorting and by spheroid formation assay from pancreatic cancer cell line Panc-1, we tested the hypothesis that nicotine induces the self-renewal of PCSCs. Nicotinic acetylcholine receptors (nAChRs) α3, α4, α5 and α7 were expressed and chronic exposure to nicotine increased the protein expression of these receptors. Immunoassays showed that PCSCs produced the stress neurotransmitters epinephrine and norepinephrine and the inhibitory neurotransmitter GABA. Chronic nicotine significantly increased the production of stress neurotransmitters and sonic hedgehog (SHH) while inducing Gli1 protein and decreasing GABA. GABA treatment inhibited the induction of SHH and Gli1. Spheroid formation and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assays showed significant nicotine-induced increases in self renewal and cell proliferation, responses blocked by GABA. Our data suggest that nicotine increases the SHH-mediated malignant potential of PCSCs and that GABA prevents these effects.
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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.