Reciprocal activation of α5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation

Zhang, Yao; Jia, Yanfei; Li, Ping; Li, Huanjie; Xiao, Dongjie; Wang, Yunshan; Ma, Xiaoli

doi:10.1016/j.jgg.2017.03.003

Cited by 39 publications

(40 citation statements)

References 45 publications

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“…We cultured A549 and H1299 cells and transfected them with si‐NC, si‐CHRNA5, si‐Stat3 or si‐CHRNA5 + si‐Stat3 fragments to study the correlation between α5‐nAChR/Stat3 and Jab1. As show in Figure A, silencing of α5‐nAChR decreased the levels of p‐Stat3 and Jab1 ( P < .05), which is generally consistent with the results of our previous study . Furthermore, silencing Stat3 decreased the levels of α5‐nAChR and Jab1 ( P < .05).…”

Section: Resultssupporting

confidence: 90%

“…ChIP assays confirmed that the CHRNA5 promoter contains Stat3 binding sites. There is a feedback loop between α5‐nAChR and Stat3 that contributes to the nicotine‐induced tumour cell proliferation . α5‐nAChR modulates lung tumour cells invasion and migration, promoting tumour metastasis .…”

Section: Discussionmentioning

confidence: 99%

“…siRNAs for CHRNA5 (encoding α5‐nAChR), Jab1, Stat3 and the negative control were obtained from GenePharma. Transient transfection of A549 and H1299 cells was performed using the Oligofectamine 2000 (Invitrogen) protocol and 5‐nmol siRNAs in RPMI supplemented with 10% FBS and no penicillin or streptomycin as described previously . Human CHRNA5 cDNA was subcloned into a pGV‐puro lentiviral vector containing the puromycin resistance to establish stable A549 and H1299 (Genechem) cell lines to induce α5‐nAChR overexpression (marked as α5‐nAChR + ).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our laboratory demonstrated that α5‐nAChR mediates nicotine‐induced lung cancer development and progression . Nicotine interacts with α5‐nAChR on the cell surface, activating the JAK2/Stat3 signalling pathways and promoting lung cancer cell proliferation . Furthermore, α5‐nAChR mediates nicotine‐induced lung cancer cell migration and invasion .…”

Section: Introductionmentioning

confidence: 99%

“…17 Nicotine interacts with α5-nAChR on the cell surface, activating the JAK2/Stat3 signalling pathways and promoting lung cancer cell proliferation. 18 Furthermore, α5-nAChR mediates nicotine-induced lung cancer cell migration and invasion. 19 Nevertheless, the mechanism by which α5-nAChR functions in lung cancer EMT remains to be elucidated.…”

mentioning

confidence: 99%

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α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

Chen

Jia

Zhang

et al. 2020

J Cellular Molecular Medi

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Recent studies have showed that α5 nicotinic acetylcholine receptor (α5‐nAChR) is closely associated with nicotine‐related lung cancer. Our previous studies also demonstrated that α5‐nAChR mediates nicotine‐induced lung carcinogenesis. However, the mechanism by which α5‐nAChR functions in lung carcinogenesis remains to be elucidated. Jab1/Csn5 is a key regulatory factor in smoking‐induced lung cancer. In this study, we explored the underlying mechanisms linking the α5‐nAChR‐Jab1/Csn5 axis with lung cancer epithelial‐mesenchymal transition (EMT) and metastasis, which may provide potential therapeutic targets for future lung cancer treatments. Our results demonstrated that the expression of α5‐nAChR was correlated with the expression of Jab1/Csn5 in lung cancer tissues and lung cancer cells. α5‐nAChR expression is associated with Jab1/Csn5 expression in lung tumour xenografts in mice. In vitro, the expression of α5‐nAChR mediated Stat3 and Jab1/Csn5 expression, significantly regulating the expression of the EMT markers, N‐cadherin and Vimentin. In addition, the down‐regulation of α5‐nAChR or/and Stat3 reduced Jab1/Csn5 expression, while the silencing of α5‐nAChR or Jab1/Csn5 inhibited the migration and invasion of NSCLC cells. Mechanistically, α5‐nAChR contributes to EMT and metastasis by regulating Stat3‐Jab1/Csn5 signalling in NSCLC, suggesting that α5‐nAChR may be a potential target in NSCLC diagnosis and immunotherapy.

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

Chen

Jia

Zhang

et al. 2020

J Cellular Molecular Medi

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α5‐nAChR and survivin: Two potential biological targets in lung adenocarcinoma

Zhang

Sun

Jia

et al. 2020

Journal Cellular Physiology

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Recent studies have shown that the overexpression of α5 nicotinic acetylcholine receptor (α5-nAChR) is associated with nicotine-related lung carcinogenesis. Survivin is one of the biomarkers of a worse prognosis for smoking-related lung cancer. The aim of this study is to investigate the association of α5-nAChR, survivin, and clinical outcomes in lung adenocarcinoma (LUAD). We analyzed the expression level and correlation of CHRNA5 (encoding α5-nAChR) and BIRC5 (encoding survivin) in LUAD with The Cancer Genome Atlas data set. The relationship between overall survival (OS) and the expression of CHRNA5 or/and BIRC5 was evaluated by the Kaplan-Meier method and Cox proportional hazards model. Moreover, our results showed that the expression of α5-nAChR mediated survivin expression in lung cancer cells and in lung tumor xenografts. Relationships between the expression of α5-nAChR and/or survivin with clinical-pathological characteristics were analyzed using LUAD tissue samples. The results showed that expression of α5-nAChR was correlated with survivin expression in vitro and in vivo. The group coexpressing α5-nAChR and survivin had a worse prognosis than other subgroups in LUAD (p < .05). In conclusion, ascertaining the expression of both α5-nAChR and survivin provides a better measure of prognosis for LUAD patients. The combined inhibition of α5-nAChR and survivin may be a promising multitargeted gene therapeutic strategy in LUAD diagnosis.

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PLEK2 mediates metastasis and invasion via α5‐nAChR activation in nicotine‐induced lung adenocarcinoma

Li,

Wang

et al. 2023

Molecular Carcinogenesis

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Evidence has shown a strong relationship between smoking and epithelial mesenchymal transition (EMT). α5‐nicotinic acetylcholine receptor (α5‐nAChR) contributes to nicotine‐induced lung cancer cell EMT. The cytoskeleton‐associated protein PLEK2 is mainly involved in cytoskeletal protein recombination and cell stretch migration regulation, which is closely related to EMT. However, little is known about the link between nicotine/α5‐nAChR and PLEK2 in lung adenocarcinoma (LUAD). Here, we identified a link between α5‐nAChR and PLEK2 in LUAD. α5‐nAChR expression was correlated with PLEK2 expression, smoking status and lower survival in vivo. α5‐nAChR mediated nicotine‐induced PLEK2 expression via STAT3. α5‐nAChR/PLEK2 signaling is involved in LUAD cell migration, invasion and stemness. Moreover, PLEK2 was found to interact with CFL1 in nicotine‐induced EMT in LUAD cells. Furthermore, the functional link among α5‐nAChR, PLEK2 and CFL1 was confirmed in mouse xenograft tissues and human LUAD tissues. These findings reveal a novel α5‐nAChR/PLEK2/CFL1 pathway involved in nicotine‐induced LUAD progression.

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Reciprocal activation of α5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation

Cited by 39 publications

References 45 publications

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

α5‐nAChR contributes to epithelial‐mesenchymal transition and metastasis by regulating Jab1/Csn5 signalling in lung cancer

α5‐nAChR and survivin: Two potential biological targets in lung adenocarcinoma

PLEK2 mediates metastasis and invasion via α5‐nAChR activation in nicotine‐induced lung adenocarcinoma

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