Betel quid extract promotes oral cancer cell migration by activating a muscarinic M4 receptor-mediated signaling cascade involving SFKs and ERK1/2

Biochemical and Biophysical Research Communications
Chien-Chih ChiuJeff Yi-Fu Chen

Abstract

Betel quid (BQ) is a widely accepted etiological factor for oral squamous cell carcinoma (OSCC) in Southeast Asia, but how BQ chewing leads to oral carcinogenesis remains to be elucidated. We have previously demonstrated that the activation of Src family kinases (SFKs) is critical for BQ-induced oral cancer cell motility. Here we investigate whether this biological effect is mediated by specific membrane receptors in oral cancer cells. We found that BQ-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cell migration could be inhibited by atropine, suggesting the involvement of the muscarinic receptor family. The enhanced activities of ERK1/2 and cell migration were significantly counteracted by PD102807, the selective antagonist of muscarinic M4 receptor. Moreover, cold BQ extract effectively competed with a known ligand, [(3)H]-N-methyl scopolamine, for binding to muscarinic M4 receptor in vitro, thereby implying that BQ could activate motility-promoting signaling pathways through direct interaction with the receptor. The requirement of muscarinic M4 receptor for BQ-induced oral cancer cell migration was demonstrated by knockdown of the receptor using RNA interference (RNAi). Remarkably, ectopic expr...Continue Reading

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Citations

Jan 15, 2013·Journal of Pharmaceutical and Biomedical Analysis·Chun-Liang TungHong-Lin Chan
Feb 18, 2014·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Wan-Chun LiKuo-Wei Chang
Feb 18, 2015·Oncotarget·Chih-Chang HungJeff Yi-Fu Chen
Oct 31, 2020·Cancers·Anna Maria Lucianò, Ada Maria Tata
Jul 1, 2021·World Journal of Clinical Oncology·Alejandro EspañolMaría Elena Sales

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