Overexpression and Activation of the α9-Nicotinic Receptor During Tumorigenesis in Human Breast Epithelial Cells

Lee, Chia Hwa; Huang, Ching Shui; Chen, Ching Shyang; Tu, Shih Hsin; Wang, Ying Jan; Chang, Yu Jia; Tam, Ka Wai; Wei, Po Li; Cheng, Tzu Chun; Chu, Jan Show; Chen, Li Ching; Wu, Chih Hsiung; Ho, Yuan Soon

doi:10.1093/jnci/djq300

Cited by 158 publications

(236 citation statements)

References 59 publications

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“…Several studies have shown NNK-triggered human breast epithelial cell transformation upon long-term (>1 mo) exposure to a low concentration of NNK (100 p.m.) (37). In addition, we recently showed that nicotine (10 mM) can induce transformation in normal breast epithelial cells (MCF-10A) upon forced expression of a9-nAChR (28). Another important concern is that nAChRs can be induced in response to nicotine, NNN, and NNK exposure, which produces a detrimental feedback effect on receptor-ligand binding signaling.…”

Section: Smoking-induced Cancer Formationmentioning

confidence: 97%

“…Since then, various studies have described nAChRs as key molecules that act as central regulators of a complex network governing growth (5,28), angiogenesis (29), metastasis (7), and apoptosis (30) during carcinogenesis in response to the tumor microenvironment. In addition, nAChRs stimulate intracellular signaling pathways in a cell-typespecific manner.…”

Section: Nachr-mediated Signaling Pathwaysmentioning

confidence: 99%

“…The a9-nAChR homopentamer was originally identified in hair cells of the inner ear, and is involved in synaptic transmission between efferent nerves and hair cells (46). a9-nAChR was found to have diverse functions in keratinocyte adhesion (47), immune response (48), neuropathic pain (49), and even breast cancer formation (28). The correlation between a9-nAChR mRNA expression level and disease outcome in breast tumor patients was evaluated in a recent study (28).…”

Section: Smoking-induced Cancer Formationmentioning

confidence: 99%

“…a9-nAChR was found to have diverse functions in keratinocyte adhesion (47), immune response (48), neuropathic pain (49), and even breast cancer formation (28). The correlation between a9-nAChR mRNA expression level and disease outcome in breast tumor patients was evaluated in a recent study (28). In that study, 186 (67.3%) of 276 paired samples expressed a9-nAChR mRNA at higher levels (mean: 7.84-fold) in breast cancer than in surrounding normal tissue.…”

Section: Smoking-induced Cancer Formationmentioning

confidence: 99%

“…Interference with a9-nAChR expression as a novel strategy for drug development In a recent study, we showed that a9-nAChR was preferentially overexpressed in human breast tumor tissue in comparison with normal tissue (28). We transformed normal breast epithelial cells (MCF-10A) by long-term nicotine treatment (10 mM, >2 mo) together with forced expression of a9-nAChR using the Tet-inducible adenovirus system.…”

Section: Nachr Antagonists As Potential Agents For Molecular Cancer Tmentioning

confidence: 99%

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Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

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103

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The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and a-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that a9-nAChR is important for breast cancer formation, and in many in vivo studies, a9-nAChR-specific antagonists (e.g., a-ImI, a-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine-and estrogeninduced breast cancer cell proliferation through inhibition of the a9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.

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Section: Smoking-induced Cancer Formationmentioning

confidence: 97%

Section: Nachr-mediated Signaling Pathwaysmentioning

confidence: 99%

Section: Smoking-induced Cancer Formationmentioning

confidence: 99%

Section: Smoking-induced Cancer Formationmentioning

confidence: 99%

Section: Nachr Antagonists As Potential Agents For Molecular Cancer Tmentioning

confidence: 99%

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Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

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103

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CRISPR‐mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line

et al. 2022

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Squamous and anaplastic thyroid cancers are the most aggressive and life‐threatening cancer types in humans, with the involvement of lymph nodes in 59% of cases and distant metastases in 26% of cases of all thyroid cancers. The median survival of squamous thyroid cancer patients is < 8 months and therefore is of high clinical concern. Here, we show that both VEGFC and VEGFR2/KDR are overexpressed in thyroid cancers, indicating that VEGF/VEGFR signaling plays a carcinogenic role in thyroid cancer development. Using CRISPR/Cas9, we established a KDR knockout (KO) SW579 squamous thyroid cancer cell line that exhibited dramatically decreased colony formation and invasion abilities (30% and 60% reduction, respectively) when compared to scrambled control cells. To validate the potential of KDR as a therapeutic target for thyroid cancers, we used the KDR RTK inhibitor sunitinib. Protein analysis and live/dead assay were performed to demonstrate that sunitinib significantly inhibited cell growth signal transduction and induced cell apoptosis of SW579 cells. These results suggest that selective targeting of KDR may have potential for development into novel anti‐cancer therapies to suppress VEGF/VEGFR‐mediated cancer development in patients with clinical advanced thyroid cancer.

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Acetylcholine in Carcinogenesis and Targeting Cholinergic Receptors in Oncology

2022

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tumor vascularization and growth. [3] Further insight into the mechanisms of neurotransmission within the tumor microenvironment may offer promising opportunities for developing novel cancer therapies.Recent preclinical and clinical research has been steadily elucidating the role of cholinergic signaling in carcinogenesis, cancer growth, and cancer metastasis. This review provides an overview of the cholinergic system and synthesizes emerging evidence of the modulatory effects of neurotransmitters on carcinogenesis. The currently postulated roles of acetylcholine in carcinogenesis are elucidated, with insight into relevant clinical trials and suggestions for future studies of cancer neuromodulation.

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Overexpression and Activation of the α9-Nicotinic Receptor During Tumorigenesis in Human Breast Epithelial Cells

Abstract: The alpha9-nAChR is important for nicotine-induced transformation of normal human breast epithelial cells.

Cited by 158 publications

References 59 publications

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

CRISPR‐mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line

Acetylcholine in Carcinogenesis and Targeting Cholinergic Receptors in Oncology

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