ArticleCancer cell international2018
M3 muscarinic acetylcholine receptors regulate epithelial-mesenchymal transition, perineural invasion, and migration/metastasis in cholangiocarcinoma through the AKT pathway.
Article in Cancer cell international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- Influence of the Cholinergic System on the Pathogenesis of Glioblastoma: Impact of the Neutrophil Granulocytes.International journal of molecular sciences · 2025Article
- 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
- Significance and mechanisms of perineural invasion in malignant tumors.Frontiers in oncology · 2025Review
- Potential antiproliferative and apoptotic effects of pilocarpine combined with TNF alpha in chronic myeloid leukemia cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Three-dimensional analysis of perineural invasion in extrahepatic cholangiocarcinoma using tissue clearing.Pathology oncology research : POR · 2023Article
- Article
- Atropine Is a Suppressor of Epithelial-Mesenchymal Transition (EMT) That Reduces Stemness in Drug-Resistant Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.Journal of clinical medicine · 2022Article
- Review
- Potential Role for Combined Subtype-Selective Targeting of MFrontiers in pharmacology · 2021Review
- Perineural Invasion and Postoperative Complications are Independent Predictors of Early Recurrence and Survival Following Curative Resection of Gastric Cancer.Cancer management and research · 2020Article
- A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma.BioMed research international · 2019Article
Corrections and comments
- Retracted
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCholangiocarcinoma is a highly malignant tumor type that is not sensitive to radiotherapy or chemotherapy due to aggressive perineural invasion and metastasis. Unfortunately, the mechanisms underlying these processes and the signaling factors involved are largely unknown. In this study, we analyzed the role of M3 muscarinic acetylcholine receptors (M3-mAChR) in cell migration, perineural invasion, and metastasis during cholangiocarcinoma.
methodsWe assessed 60 human cholangiocarcinoma tissue samples and 30 normal biliary tissues. Immunohistochemical staining was used to detect M3-mAChR expression and the relationship between expression and clinical prognosis was evaluated. The biological functions of M3-mAChR in cholangiocarcinoma cell migration, perineural invasion, and epithelial-mesenchymal transition (EMT) were investigated using the human cholangiocarcinoma cell lines FRH0201 and RBE in conjunction with various techniques, including agonist/antagonist treatment, RNA interference, M3-mAChR overexpression, dorsal root ganglion co-culturing, immunohistochemistry, western blotting, etc.
resultsM3-mAChR were highly expressed in cholangiocarcinoma tissue and expression was closely related to differentiation and lymphatic metastasis, affecting patient survival. Treatment with the M3-mAChR agonist pilocarpine and M3-mAChR overexpression significantly promoted migration and perineural invasion, while the M3-mAChR antagonist atropine blocked these effects. Similarly, M3-mAChR knock-down also weakened cell migration and perineural invasion. The expression of phosphatase and tensin homolog, AKT, E-cadherin, vimentin, and Snail, which are components of the phosphatidylinositol 3-kinase/AKT signaling pathway and EMT, were altered by pilocarpine, and these effects were again blocked by atropine. Notably, AKT knock-down decreased M3-mAChR expression and reversed the downstream effects of this receptor.
conclusionsM3-mAChR are involved in tumor cell migration, perineural invasion, and EMT during cholangiocarcinoma, and these effects are modulated via the AKT signaling pathway.
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