Contribution of the α5 nAChR Subunit and α5SNP to Nicotine-Induced Proliferation and Migration of Human Cancer Cells

Papapostolou, Irida; Ross‐Kaschitza, Daniela; Bochen, Florian; Peinelt, Christine; Maldifassi, María Constanza

doi:10.3390/cells12152000

Cited by 4 publications

(1 citation statement)

References 98 publications

(160 reference statements)

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“…Activation of α7nAchRs by nicotine contributes to CRC cell proliferation via MAPK/ERK signaling [156,158], inhibition of apoptosis [159], stimulation of CRC cell migration by fibronectin, MMP-1, -2, and -9 induction [158,160], and angiogenesis [157]. Similarly, nicotine-driven activation of α5nAchRs leads to increased cancer cell proliferation and migration through epithelialto-mesenchymal transition [161]. Paradoxically, Fei at al.…”

Section: Colorectal Cancermentioning

confidence: 99%

Cholinergic Mechanisms in Gastrointestinal Neoplasia

Sampaio Moura,

Schledwitz,

Alizadeh

et al. 2024

IJMS

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Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes.

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Section: Colorectal Cancermentioning

confidence: 99%

Cholinergic Mechanisms in Gastrointestinal Neoplasia

Sampaio Moura,

Schledwitz,

Alizadeh

et al. 2024

IJMS

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The Diagnostic and Prognostic Value of Neurotransmitter Receptor-Related Genes in Colon Adenocarcinoma

Hu,

Wu,

Dong

et al. 2023

Mol Biotechnol

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Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

Fu,

Shen,

Wang

et al. 2024

Sig Transduct Target Ther

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Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a “neural addiction” property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca2+-mediated activation of Ca/calmodulin-dependent protein kinases (CAMKII). In addition, acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor (BDNF), which formed a feedforward acetylcholine-BDNF axis to promote ICC progression. KN93, a small-molecule inhibitor of CAMKII, significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells. Above all, Acetylcholine/CHRNA5 axis increased the expression of β-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKII/GSK3β signaling, and the CAMKII inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

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Contribution of the α5 nAChR Subunit and α5SNP to Nicotine-Induced Proliferation and Migration of Human Cancer Cells

Cited by 4 publications

References 98 publications

Cholinergic Mechanisms in Gastrointestinal Neoplasia

Cholinergic Mechanisms in Gastrointestinal Neoplasia

The Diagnostic and Prognostic Value of Neurotransmitter Receptor-Related Genes in Colon Adenocarcinoma

Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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