Abstract A135: IFIT1 and 3 modulate the drug sensitivity in human oral squamous cell carcinoma cells

Abstract Interferon-induced protein with tetratricopeptide repeats (IFITs) family, well-known interferons stimulated genes, have 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: IFIT1, IFIT2, IFIT3, and IFIT5 in humans. We have previously shown that IFIT2 inhibits oral squamous cell carcinoma (OSCC) metastasis. Alternatively, our recent studies revealed the involvement of IFIT1 and IFIT3 in the progression of OSCC. The study on IFIT5 was far from adequate. The failure of chemotherapy or targeted therapy was often associated with the intrinsic or acquired drug resistance. In the present study, we are investigating the role of IFIT1 and IFIT3 genes on drug resistance in OSCC cells. Our results showed that ectopic expression of IFIT1 and IFIT3 proteins in OSCC cells significantly increased the resistance to cisplatin, whereas they became highly susceptible to gefitinib, a tyrosine kinase inhibitor. Consistently, silencing of IFIT1 and IFIT3 by shRNA enhanced the sensitivity to cisplatin but resulted in increased resistance to gefitinib. We further demonstrated that enhanced expression of IFIT1 and IFIT3 significantly increased the levels of activated forms of AKT (p-AKT) and EGFR (p-EGFR), suggesting that AKT and EGFR signaling could be activated by IFIT1 and IFIT3. Our present results indicate that IFIT1 and IFIT3 may serve as a marker for precisely choosing right therapeutic agents for the treatment of patients with OSCC. Citation Format: Vijaya Kumar Pidugu, Mei-Maan Wu, Chung-Ji Liu, Te-Chang Lee. IFIT1 and 3 modulate the drug sensitivity in human oral squamous cell carcinoma cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A135.