ArticleCancer biology & therapy2015
Blocking M2 muscarinic receptor signaling inhibits tumor growth and reverses epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC).
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
- The Role of the Nervous System in Lung Disease.Current neurology and neuroscience reports · 2026Review
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Neurotransmitter Regulatory Networks: A New Perspective on Cancer Therapy.Biomolecules · 2025Review
- The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets.Molecular cancer · 2025Review
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- OCTN1 mediates acetylcholine transport in the A549 lung cancer cells: possible pathophysiological implications.Frontiers in molecular biosciences · 2024Article
- Schwann cells in the normal and pathological lung microenvironment.Frontiers in molecular biosciences · 2024Review
- Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.Neuroscience bulletin · 2023Review
- The Role of the Acetylcholine System in Common Respiratory Diseases and COVID-19.Molecules (Basel, Switzerland) · 2023Review
- Nintedanib-αVβ6 Integrin Ligand Conjugates Reduce TGFInternational journal of molecular sciences · 2023Article
- The Hyperglycemia Stranglehold Stifles Cutaneous Epithelial‒Mesenchymal Plasticity and Functional Wound Closure.The Journal of investigative dermatology · 2021Article
- Agrin expression is correlated with tumor development and poor prognosis in cholangiocarcinoma.The Journal of international medical research · 2021Article
- Role of the parasympathetic nervous system in cancer initiation and progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.Cardiovascular diabetology · 2021Article
- The Combination of the M2 Muscarinic Receptor Agonist and Chemotherapy Affects Drug Resistance in Neuroblastoma Cells.International journal of molecular sciences · 2020Article
- Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System.Biomolecules · 2020Article
- Article
- Epithelial-to-mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy.Thoracic cancer · 2019Article
- Nicotine promotes the development of non-small cell lung cancer through activating LINC00460 and PI3K/Akt signaling.Bioscience reports · 2019Article
- Mining and validating the expression pattern and prognostic value of acetylcholine receptors in non-small cell lung cancer.Medicine · 2019Observational
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancers express non-neuronal, cholinergic autoparacrine loop, which facilitates tumor growth. Interruption of M3 muscarinic cholinergic signaling has been reported to inhibit small cell lung cancer (SCLC) growth. The purpose of this study is to investigate if blocking autoparacrine muscarinic cholinergic signaling could inhibit non-small cell lung cancer (NSCLC) growth and possible underlying mechanisms. Our results showed that PC9 and A549 cells expressed all 5 subtypes of muscarinic receptor (mAChR) and blocking M2 mAChR (M2R) signaling using selective antagonist methoctramine or short hairpin RNA (shRNA) inhibited tumor cell proliferation in vitro and in vivo. Consistent with AChR agonists stimulating p44/42 MAPK (Erk1/2) and Akt phosphorylation, blocking M2R signaling decreased MAPK and Akt phosphorylation, indicating that non-neuronal ACh functions as an autoparacrine growth factor signaling in part through activation of M2R and downstream MAPK and Akt pathways. Importantly, further studies revealed that blocking M2R signaling also reversed epithelial-mesenchymal transition (EMT) in vitro and in vivo, indicating that non-neuronal ACh promotes EMT partially through activation of M2R. These findings demonstrate that M2R plays a role in the growth and progression of NSCLC and suggest M2R antagonists may be an efficacious adjuvant therapy for NSCLC.
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