ArticleAngiogenesis2024
The angiogenic role of the alpha 9-nicotinic acetylcholine receptor in triple-negative breast cancers.
Article in Angiogenesis, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Article
- The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.Marine drugs · 2026Review
- The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.BMC medicine · 2026Review
- Nerves Stimulate Cross-talk Between Gastric Cancer and Group 3 Innate Lymphoid Cells to Enhance Immunosuppression.Cancer research · 2026Article
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Nicotinic Acetylcholine Receptor Pathways in Cancer: From Psychiatric Clues to Therapeutic Opportunities.Cancer reports (Hoboken, N.J.) · 2025Review
- 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
- Nicotine promotes the progression and metastasis of non-small cell lung cancer by modulating the OTUB1-c-Myc-EZH2 axis.Acta pharmacologica Sinica · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Nicotine acts as an angiogenic factor by stimulating endogenous cholinergic pathways. Several subtypes of nicotinic acetylcholine receptors (nAChRs) have been demonstrated to be closely correlated to the formation and progression of different types of cancers. Recently, several studies have found that nicotinic acetylcholine receptors α9 (α9-nAChRs) are highly expressed in breast tumors, especially in tumors derived from patients diagnosed at advanced stages. In vitro studies have demonstrated that activation of α9-nAChRs is associated with increased proliferation and migration of breast cancer. To study the tumor-promoting role of α9-nAChRs in breast cancers, we generated a novel anti-α9-nAChR and methoxy-polyethylene glycol (mPEG) bispecific antibody (α9 BsAb) for dissecting the molecular mechanism on α9-nAChR-mediated tumor progression. Unexpectedly, we discovered the angiogenic role of α9-nAChR in nicotine-induced neovascularization of tumors. It revealed α9 BsAbs reduced nicotine-induced endothelial cell tube formation, blood vessel development in Matrigel plug assay and angiogenesis in microtube array membrane murine model (MTAMs). To unbraid the molecular mechanism of α9-nAChR in nicotine-mediated angiogenesis, the α9 BsAbs were applied and revealed the inhibitory roles in nicotine-induced production of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor A (VEGF-A), phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2), vascular endothelial growth factor receptor 2 (VEGFR2) and matrix metalloproteinase-9 (MMP9) from triple-negative breast cancer cells (MDA-MB-231), suggesting α9-nAChRs played an important role in nicotine-induced angiogenesis. To confirm our results, the shRNA targeting α9-nAChRs was designed and used to silence α9-nAChR expression and then evaluated the angiogenic role of α9-nAChRs. The results showed α9 shRNA also played an inhibitory effect in blocking the nicotine-induced angiogenic signaling. Taken together, α9-nAChR played a critical role in nicotine-induced angiogenesis and this bispecific antibody (α9 BsAb) may serve as a potential therapeutic candidate for treatments of the α9 positive cancers.
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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.