Abstract C29: Association of interferon-induced protein with tetratricopeptide repeats 1 gene family with human papilloma virus infection in patients with oral squamous cell carcinoma

Abstract

Abstract Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) gene family is one of most responsive interferon-stimulated gene families. Four members have been characterized in humans, namely, IFIT1, IFIT2, IFIT3, and IFIT5. The encoded proteins mediate a variety of protein—protein interactions by tetratricopeptide repeat helix-turn-helix motifs to modulate on cellular functions, such as translation initiation, double-stranded RNA-induced signaling, cell proliferation and migration. We have previously demonstrated that IFIT2 silencing activates atypical PKC signaling and induces epithelial-mescenchymal transition (EMT), cell migration, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells in cultured or animal models. Our results also showed that IFIT2 is potentially a prognosis biomarker of patients with OSCC. In the present study, we further explore the roles of IFIT1 family proteins involved in the regulatory mechanism of metastasis in OSCC cells. We first confirmed that the proteins of various IFIT1 family members are significantly induced by interferon in a dose-dependent manner. We further characterized the expression of IFIT1, IFIT3, and IFIT5 proteins in patients with OSCC. Our present results revealed that most OSCC tumor tissues expressed a variety of amounts of IFIT2 proteins by immunohistochemical analysis. Although the expression levels of IFIT1 and IFIT3 were relatively lower than IFIT2, we observed a close association between IFIT1 and IFIT3 protein expression in OSCC patient-derived tumor specimens. Numerous studies have pointed out that human papillomavirus (HPV) infection is associated with a high risk of oral cancer. Among these 4 IFIT1 family members, we preliminarily demonstrated a well correlation between HPV E6 and IFIT5 protein expression in tumor specimens of OSCC patients, implying a critical role of IFIT5 in response of HPV infection. Accordingly, our present studies implicate that all IFIT1 family are activated by interferon but each member apparently participates in different cellular activities. Their roles involving in OSCC metastasis warrant our further investigation. Citation Format: Ai-Hsin Yen, Kuo-chu Lai, Ying-Chen Chen, Chung-Ji Liu, Kuo-Wei Chang, Te-Chang Lee. Association of interferon-induced protein with tetratricopeptide repeats 1 gene family with human papilloma virus infection in patients with oral squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C29.