Abstract 40: Association of Interferon-induced protein with tetratricopeptide repeats 1 and 3 expression with regional metastasis and drug resistance in oral squamous cell carcinoma

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) gene family, consisting of 4 members (IFIT1, IFIT2, IFIT3, and IFIT5) in humans, is one of most responsive interferon-stimulated gene families. We have previously demonstrated that IFIT2 silencing activates atypical PKC signaling and induces epithelial-mescenchymal transition, cell migration, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells in cultured or animal models. These results implicate that IFIT2 is potentially a prognosis biomarker of patients with OSCC. In the present study, we further explore the roles of other IFIT1 family proteins involved in the regulatory mechanism of metastasis and drug resistance in OSCC cells. We determined the expression levels of IFIT1 gene family proteins in 82 patients with OSCC by immunohistochemical technique. Our present results revealed a close association between IFIT1 and IFIT3 protein expression in OSCC patient-derived tumor specimens (p < 0.001). However, the expression levels of IFIT1 or IFIT3 did not have a correlation with that of IFIT2 in tumor tissues. Intriguingly, IFIT5 was the only member of IFIT1 family displayed a well correlation with HPV E6 protein expression. Furthermore, we found that the expression levels of IFIT1 and IFIT3 were positively associated with age as well as regional lymph node metastasis status, whereas they were marginally and inversely associated with the differentiation features. We further demonstrated that IFIT1 and IFIT3 protein expression-induced by pre-treatment or co-treatment with IFN-β in Ca9-22 cells increased their resistance to Cisplatin and 5-flurouracil (5-FU). Silencing of IFIT1 and IFIT3 protein expression in SCC-25 cells by its specific shRNA, respectively, increased their susceptibility to Cisplatin and 5-FU. Since our present studies reveal that enhanced IFIT1 and IFIT3 expression associate with regional lymph node metastasis and drug resistance to Cisplatin and 5-FU, the roles of IFIT1 and IFIT3 expression associated with the clinicopathologic development in OSCC patients warrant our further investigation. Citation Format: Ai-Hsin Yen, Ying-Chen Chen, Vijaya Kumar Pidugu, Chung-Ji Liu, Te-Chang Lee. Association of Interferon-induced protein with tetratricopeptide repeats 1 and 3 expression with regional metastasis and drug resistance in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014