Oral cancer is characterized as prolonged exposure to potential risk factors, including tobacco use or cigarette smoking. However, the underlined mechanism of tobacco leads to cancer is still largely unknown. To shed light on the molecular basis of tobacco induced oral carcinogenesis, we established three sublines of oral cancer cells chronically treated with nicotine (IC30 dose for 3 months). Phenotypic characterization showed that the sublines were tolerant to nicotine, increased cell invasion and migration abilities, along with the altered expressions of epithelial-mesenchymal transition markers. The transcriptomic profiling analysis was performed between parental and the subline cells to global survey and identify nicotine induced genes. Heretical clustering analysis reveals that 1004 genes were differentially expressed, in which 28% of the genes associated with cell mobility. Total of 13 genes were confirmed by RT-PCR assay that over-expressed in the nicotine sublines. ASAP1 was significantly increased in all 3 cell lines, and it was selected for further studied. Knockdown ASAP1 expressions by shRNA reduced nicotine induced cell migration (to 60% ∼ 80%) and invasion (to 55% ∼ 60%) abilities. This ASAP1 silencing further inhibited nicotine- induced MMP2 enzyme activity. Clinical study also supported this finding that ASAP1 was significantly elevated in the oral cancer tissues from patients with smoking habits (P=0.042) but not in the cancer patients without smoking (P=0.714). We therefore concluded that tobacco contributes to oral cancer by the promotion of cell migration and invasion, which was at least in part, through ASAP1 associated signaling pathway.
Citation Format: Chang Hsu Chiang. Nicotine contributes to oral cancer by promotion of cell invasion through ASAP1 signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3585. doi:10.1158/1538-7445.AM2013-3585