Abstract 1428: Upregulation of IKBKE promotes glioma cell migration and invasion by phosphorylation of Snail

Abstract

Abstract IKBKE is a member of IκB kinase (IKK) family. Previous studies have shown that IKBKE is an oncogene in breast and ovarian cancer. In this study, we demonstrate that IKBKE is frequently upregulated in human glioma and regulates cell invasion, a process that causes incurable surgery for glioma. Increase expression of IKBKE was detected in 7 of 11 glioma cell lines and 41 of 57 primary tumors examined, which closely correlates with high grade tumors and patient poor overall survival. Further, ectopic expression of IKBKE induces and knockdown of IKBKE decreases cell migration and invasion. Notably, E-cadherin protein and mRNA levels were inversely regulated by IKBKE. Moreover, we demonstrated that IKBKE directly binds and phosphorylates Snail at Ser-165. The phosphorylation of Snail induces its stability and nuclear translocation and represses E-cadherin expression. Taken together, these findings indicate that IKBKE could play a pivotal role in gliomagenesis and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1428. doi:10.1158/1538-7445.AM2011-1428