The α9 nicotinic acetylcholine receptor mediates nicotine-induced pd-l1 expression and regulates melanoma cell proliferation and migration

Hai Duong Nguyen, You Cheng Liao, Yuan Soon Ho, Li Ching Chen, Hui Wen Chang, Tzu Chun Cheng, Donald Liu, Woan Ruoh Lee, Shing Chuan Shen, Chih Hsiung Wu, Shih Hsin Tu

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4 引文 斯高帕斯(Scopus)

摘要

Cigarette smoking is associated with an increased risk of melanoma metastasis. Smokers show higher PD-L1 expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Here, we investigate whether nicotine, a primary constituent of tobacco, induces PD-L1 expression and promotes melanoma cell proliferation and migration, which is mediated by the α9 nicotinic acetylcholine receptor (α9-nAChR). α9-nAChR overexpression in melanoma using melanoma cell lines, human melanoma tissues, and assessment of publicly available databases. α9-nAChR expression was significantly correlated with PD-L1 expression, clinical stage, lymph node status, and overall survival (OS). Overexpressing or knocking down α9-nAChR in melanoma cells up-or downregulated PD-L1 expression, respectively, and affected melanoma cell proliferation and migration. Nicotine-induced α9-nAChR activity promoted melanoma cell proliferation through stimulation of the α9-nAChR-mediated AKT and ERK signaling pathways. In addition, nicotine-induced α9-nAchR activity promoted melanoma cell migration via activation of epithelial-mesenchymal transition (EMT). Moreover, PD-L1 expression was upregulated in melanoma cells after nicotine treatment via the transcription factor STAT3 binding to the PD-L1 promoter. These results highlight that nicotine-induced α9-nAChR activity promotes melanoma cell proliferation, migration, and PD-L1 upregulation. This study may reveal important insights into the mechanisms.
原文英語
文章編號1991
期刊Cancers
11
發行號12
DOIs
出版狀態已發佈 - 十二月 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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