Abstract 3933: Characterization of oncogenic activity of interferon-induced protein with tetratricopeptide repeats 1 and 3 in human oral squamous cell carcinoma progression

Abstract

Abstract Interferon-induced protein with tetratricopeptide repeats (IFITs) family has multiple tetratricopeptide repeats with helix-turn-helix structural motifs that mediate a variety of protein-protein interactions. There are four IFIT genes that have been identified namely, ISG56/IFIT1, ISG54/IFIT2, ISG60/IFIT3, and ISG58/IFIT5. IFIT proteins have been documented to involve in a variety of cellular functions, such as cell proliferation, migration, virus-induced translation initiation, replication and double-stranded RNA signaling. Our previous study has demonstrated that IFIT2 inhibits oral squamous cell carcinoma (OSCC) metastasis. However, little is known about IFIT1 and IFIT3 in the progression of OSCC. In the present study, we are investigating the functional role of IFIT1 and IFIT3 genes in OSCC tumor progression. Immunohistochemical analysis of 147 patients derived tumor specimens with OSCC revealed a strong correlation between IFIT1 and IFIT3 proteins (p<0.001). Clinicoplathological characteristics correlation of IFIT1 and IFIT3 expression levels were positively associated with regional lymph node invasion and nerve invasion. IFIT1 was also associated with venous invasion. Ectopic expression of IFIT1 and IFIT3 proteins in Ca9-22 and SAS cells inducing PKC, EGFR, and AKT activation, resulting in OSCC cells resistance to cisplatin but highly susceptible to tyrosine kinase inhibitor gefitinib, whereas IFIT1 and IFIT3 knockdown SCC25 cells have shown opposite effect. Interestingly, IFIT1 and IFIT3 expression is associated with enhanced cell invasion activity and altered expression of epithelial-mesenchymal transition markers. These data suggested that IFIT1 and IFIT3 may serve as potential biomarkers for the OSCC treatment. The study on how IFIT1 and IFIT3 cause PKC, EGFR, and AKT activation and resistance to DNA damaging agents is ongoing. Our further investigations may explain the molecular signaling mechanism of IFIT1 and IFIT3 in OSCC tumor progression. Citation Format: Vijaya Kumar Pidugu, Ai-Hsin Yen, Ying-Chen Chen, Mei-Maan Wu, Chung-Ji Liu, Te-Chang Lee. Characterization of oncogenic activity of interferon-induced protein with tetratricopeptide repeats 1 and 3 in human oral squamous cell carcinoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3933. doi:10.1158/1538-7445.AM2017-3933