Arecoline promotes migration of A549 lung cancer cells through activating the EGFR/SRC/FAK pathway

Chih Hsiang Chang, Mei Chih Chen, Te Huan Chiu, Yu Hsuan Li, Wan Chen Yu, Wan Ling Liao, Muhammet Oner, Chang Tze Ricky Yu, Chun Chi Wu, Tsung Ying Yang, Chieh Lin Jerry Teng, Kun Yuan Chiu, Kun Chien Chen, Hsin Yi Wang, Chia Herng Yue, Chih Ho Lai, Jer Tsong Hsieh, Ho Lin

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Arecoline is the primary alkaloid in betel nuts, which are known as a risk factor for oral submucosal fibrosis and oral cancer. Lung cancer is a severe type of carcinoma with high cell motility that is difficult to treat. However, the detailed mechanisms of the correlation between Arecoline and lung cancer are not fully understood. Here, we investigated the effect of Arecoline on migration in lung cancer cell lines and its potential mechanism through the muscarinic acetylcholine receptor 3 (mAChR3)-triggered EGFR/Src/FAK pathway. Our results indicate that different concentrations of Arecoline treatment (10 µM, 20 µM, and 40 µM) significantly increased the cell migration ability in A549 and CL1-0 cells and promoted the formation of the filamentous actin (F-actin) cytoskeleton, which is a crucial element for cell migration. However, migration of H460, CL1-5, and H520 cell lines, which have a higher migration ability, was not affected by Arecoline treatment. The EGFR/c-Src/Fak pathway, which is responsible for cell migration, was activated by Arecoline treatment, and a decreased expression level of E-cadherin, which is an epithelial marker, was observed in Arecoline-treated cell lines. Blockade of the EGFR/c-Src/Fak pathway with the inhibitors of EGFR (Gefitinib) or c-Src (Dasatinib) significantly prevented Arecoline-promoted migration in A549 cells. Gefitinib or Dasatinib treatment significantly disrupted the Arecoline-induced localization of phospho-Y576-Fak during focal adhesion in A549 cells. Interestingly, Arecoline-promoted migration in A549 cells was blocked by a specific mAChR3 inhibitor (4-DAMP) or a neutralizing antibody of matrix metalloproteinase (MMP7 or Matrilysin). Taken together, our findings suggest that mAChR3 might play an essential role in Arecoline-promoted EGFR/c-Src/Fak activation and migration in an A549 lung cancer cell line.

Original languageEnglish (US)
Article number185
Issue number4
StatePublished - Apr 2019


  • Arecoline
  • EGFR
  • FAK
  • Lung cancer cells
  • MAchR3
  • SRC

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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