α5‐nAChR modulates melanoma growth through the Notch1 signaling pathway

Meng, Xianguang; Qin, Guojing; An, Yunhe; Zhang, Qianqian; Cheng, Xiaoyan; Huang, Shuhong

doi:10.1002/jcp.29435

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…EMT is regarded as a critical step in tumor invasion and metastasis [36]. A previous study suggested that CHRNA5 could regulate the migration and invasion ability of melanoma cells [23]. Similarly, our study indicated that CHRNA5 could enhance the invasion and metastasis ability of HCC by regulating EMT-associated genes.…”

Section: Discussionsupporting

confidence: 62%

“…CHRNA5, upregulated in breast cancer, was identified as the secondary estrogen signaling network and exhibited prognostic value in breast cancer [22]. In melanoma, CHRNA5 was reported to modulate cancer growth by regulating the Notch1 signaling pathway [23]. Another study found that CHRNA5 could promote radioresistance via regulating E2F transcription factor activity in oral squamous cell carcinoma [24].…”

Section: Introductionmentioning

confidence: 99%

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CHRNA5 Contributes to Hepatocellular Carcinoma Progression by Regulating YAP Activity

et al. 2022

Pharmaceutics

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Hepatocellular carcinoma (HCC) is a major health concern worldwide. A better understanding of the mechanisms underlying the malignant phenotype is necessary for developing novel therapeutic strategies for HCC. Signaling pathways initiated by neurotransmitter receptors, such as α5-nicotinic acetylcholine receptor (CHRNA5), have been reported to be implicated in tumor progression. However, the functional mechanism of CHRNA5 in HCC remains unclear. In this study, we explored the role of CHRNA5 in HCC and found that CHRNA5 expression was increased in human HCC tissues and positively correlated with the T stage (p < 0.05) and AJCC phase (p < 0.05). The KM plotter database showed that the high expression level of CHRNA5 was strongly associated with worse survival in HCC patients. Both in vitro and in vivo assays showed that CHRNA5 regulates the proliferation ability of HCC by regulating YAP activity. In addition, CHRNA5 promotes the stemness of HCC by regulating stemness-associated genes, such as Nanog, Sox2 and OCT4. Cell migration and invasion assays demonstrated that CHRNA5 significantly enhanced the metastasis of HCC by regulating epithelial–mesenchymal transition (EMT)-associated genes. Furthermore, we found that CHRNA5 regulates the sensitivity of sorafenib in HCC. Our findings suggest that CHRNA5 plays a key role in the progression and drug resistance of HCC, and targeting CHRNA5 may be a strategy for the treatment of HCC.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

CHRNA5 Contributes to Hepatocellular Carcinoma Progression by Regulating YAP Activity

et al. 2022

Pharmaceutics

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“…Consistently, a recent report also demonstrated the involvement of α5-nAChR in the EMT process and tumor metastasis through regulating the Jab1/Csn5 signaling in lung cancer [ 45 ]. Another study revealed the role of α5-nAChR in regulating cell proliferation and migration in melanoma cells [ 46 ]. We further showed that α5-nAChR is essential of low-dose nicotine-induced EGFR phosphorylation as 100 nM nicotine had limited effect on phosphorylated EGFR when α5-nAChR was knocked down.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression

Wang

Hsu

Liu

et al. 2020

IJMS

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Nicotine in tobacco smoke is considered carcinogenic in several malignancies including lung cancer. The high incidence of lung adenocarcinoma (LAC) in non-smokers, however, remains unexplained. Although LAC has long been less associated with smoking behavior based on previous epidemiological correlation studies, the effect of environmental smoke contributing to low-dose nicotine exposure in non-smoking population could be underestimated. Here we provide experimental evidence of how low-dose nicotine promotes LAC growth in vitro and in vivo. Screening of nicotinic acetylcholine receptor subunits in lung cancer cell lines demonstrated a particularly high expression level of nicotinic acetylcholine receptor subunit α5 (α 5-nAChR) in LAC cell lines. Clinical specimen analysis revealed up-regulation of α 5-nAChR in LAC tumor tissues compared to non-tumor counterparts. In LAC cell lines α 5-nAChR interacts with epidermal growth factor receptor (EGFR), positively regulates EGFR pathway, enhances the expression of epithelial-mesenchymal transition markers, and is essential for low-dose nicotine-induced EGFR phosphorylation. Functionally, low-dose nicotine requires α 5-nAChR to enhance cell migration, invasion, and proliferation. Knockdown of α 5-nAChR inhibits the xenograft tumor growth of LAC. Clinical analysis indicated that high level of tumor α 5-nAChR is correlated with poor survival rates of LAC patients, particularly in those expressing wild-type EGFR. Our data identified α 5-nAChR as an essential mediator for low-dose nicotine-dependent LAC progression possibly through signaling crosstalk with EGFR, supporting the involvement of environmental smoke in tumor progression in LAC patients.

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“…The nicotinic receptors have been studied in melanoma cells, highlighting the presence of multiple subunits such as α5/α9 / α3/ β4 [123,124,126,127]. Alpha-5 nicotinic receptors (α5-nAChR), one of the homopentameric nicotinic receptors, have been identified in different forms of solid tumors.…”

Section: The Nicotinic Receptors In Melanomamentioning

confidence: 99%

“…Alpha-5 nicotinic receptors (α5-nAChR), one of the homopentameric nicotinic receptors, have been identified in different forms of solid tumors. Performing an immunocytochemical analysis, it has been demonstrated that the expression of α5-nAChR is significantly increased in human melanoma tissue and melanoma cell lines, compared with normal human skin tissue [123]. The mechanism of action has been identified very recently; via the knockdown of the α5-nAChR expression in melanoma cells, it has been demonstrated that this receptor positively modulates cell proliferation, migration, and invasion.…”

Section: The Nicotinic Receptors In Melanomamentioning

confidence: 99%

Functional Characterization of Cholinergic Receptors in Melanoma Cells

Luciano

Tata

2020

Cancers

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In the last two decades, the scientific community has come to terms with the importance of non-neural acetylcholine in light of its multiple biological and pathological functions within and outside the nervous system. Apart from its well-known physiological role both in the central and peripheral nervous systems, in the autonomic nervous system, and in the neuromuscular junction, the expression of the acetylcholine receptors has been detected in different peripheral organs. This evidence has contributed to highlight new roles for acetylcholine in various biological processes, (e.g., cell viability, proliferation, differentiation, migration, secretion). In addition, growing evidence in recent years has also demonstrated new roles for acetylcholine and its receptors in cancer, where they are involved in the modulation of cell proliferation, apoptosis, angiogenesis, and epithelial mesenchymal transition. In this review, we describe the functional characterization of acetylcholine receptors in different tumor types, placing attention on melanoma. The latest set of data accessible through literature, albeit limited, highlights how cholinergic receptors both of muscarinic and nicotinic type can play a relevant role in the migratory processes of melanoma cells, suggesting their possible involvement in invasion and metastasis.

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α5‐nAChR modulates melanoma growth through the Notch1 signaling pathway

Cited by 14 publications

References 22 publications

CHRNA5 Contributes to Hepatocellular Carcinoma Progression by Regulating YAP Activity

CHRNA5 Contributes to Hepatocellular Carcinoma Progression by Regulating YAP Activity

Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression

Functional Characterization of Cholinergic Receptors in Melanoma Cells

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