Abstract 3958: IL-6 stimulates cell motility in squamous cell carcinoma of head and neck (SCCHN) cells through CK2 phosphorylation and stabilization of TWIST

Abstract

Abstract Squamous cell carcinoma of head and neck (SCCHN) is the tenth most common cancer in the world. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years. Therefore new targets for therapy are needed, and to this end we are studying signaling pathways activated by IL-6 which we have found stimulates cell migration and soft agar growth in SCCHN. Our data show that IL-6 increases TWIST expression in a transcription-independent mechanism in many SCCHN cell lines. Further investigation reveals TWIST can be phosphorylated upon IL-6 treatment. By computation prediction (http://hits.isb-sib.ch/cgi-bin/PFSCAN), we found that TWIST has a putative phosphorylation site for casein kinase 2 (CK2) suggesting that this kinase could serve as a link between IL-6 stimulation and Twist stability. To test this hypothesis, we used a CK2 inhibitor and shRNA to CK2 and found that these interventions inhibited IL-6 stimulation of TWIST stability. In addtion, mutation of the putative CK2 phosphorylation site (S18/S20) in TWIST decreased the amount of phospho- ATP incorporated by TWIST in an in vitro kinase assay and altered TWIST stability. In soft agar colony forming assays, the CK2 inhibitor, DMAT, was found to decrease the number of IL-6 stimulated colonies formed by SCCHN cells. To our knowledge, this is the first report to identify the importance of IL-6 stimulated CK2 phosphorylation of TWIST in SCCHN and supports the previous findings from other researchers. As CK2 inhibitors are currently under phase I clinical trials, our findings indicate that CK2 may be a viable therapeutic target in SCCHN. Therefore, further pre-clinical studies of this inhibitor are underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3958.