To investigate the effects and the possible underlying mechanisms of nicotine stimulation on tongue squamous cell carcinoma (TSCC) progression, a TSCC cell line Cal27 and 34 samples of paraffin-embedded TSCC were examined. Immunofluorescence, western blot analysis, and TOP/FOP flash, CCK-8, wound healing and Transwell invasion assays were used to evaluate Cal27 in response to nicotine stimulation. We also investigated expression levels of related proteins of Wnt/β-catenin and Wnt/PCP pathways in paraffin-embedded TSCC samples with or without a history of smoking by immunohistochemistry. Nicotine stimulation can promote proliferation, migration, and invasion of TSCC cells in vitro, downregulate E-cadherin, and activate the Wnt/β-catenin and Wnt/PCP pathways, which could be antagonized by the α7 nicotine acetylcholine receptor (α7 nAChR) inhibitor α-BTX. Moreover, the expression levels of β-catenin, Wnt5a and Ror2 were higher in TSCC patients with a history of smoking than those without a history of smoking. Our results suggest nicotine may promote tongue squamous carcinoma cells progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways and may play a significant role in the progression and metastasis of smoking-related TSCC.
Keywords: Wnt/PCP pathway; Wnt/β-catenin pathway; nicotine; tongue squamous cell carcinoma.