Abstract
Abstract Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) is one of most responsive interferon-stimulated genes to interferons, viruses, and a variety of agents. However, the biological functions of IFIT2 are poorly understood. Our previous study showed that IFIT2 overexpression was frequently found in tumor tissues of oral squamous cell carcinoma (OSCC). Besides, enhanced IFIT2 expression was inversely associated with poor patient survival. In cultured cell system, we demonstrated that depletion of IFIT2 expression in OSCC cell lines significantly enhanced the motility of cells. In this study, experiments were conducted to explore the underlying mechanisms by which IFIT2 depletion enhanced migration of OSCC cells. We first established stable IFIT2 knockdown and non-silencing control cells by lentivirus transduction system. Our results showed that stable IFIT2 knockdown cells displayed elongated spindle-like morphology, F-actin reorganization, and loss of epithelial markers, such as E-cadherin and keratin 18, as compared to control cells, suggesting the involvement of IFIT2 in epithelial-mesenchymal transition and F-actin cytoskeleton organization. While stable IFIT2 knockdown cells exhibited enhanced cell motility and invasion as compared to control cells, we found that PI3K/Akt or PKC inhibitors significantly inhibited migration of stable IFIT2 knockdown OSCC cells. Notably, PKCζ pseudosubstract significantly abolished IFIT2 depletion-induced migration. Furthermore, atypical PKC phosphorylation (Thr410/403) was enhanced in IFIT2-silencing cells compared to that of control cells. Furthermore, among 25 metastatic OSCC patients, the median survival was 57.4 months in patients expressed high levels of IFIT2 (IFIT2 ≥ 50), whereas the median survival drastically reduced to 13.6 months in patients expressed low IFIT2 (IFIT2 < 50). Taken together, our results revealed that atypical PKC signaling may involve in enhanced migration of IFIT2 knockdown OSCC cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1398. doi:10.1158/1538-7445.AM2011-1398
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