Abstract 4416: IKBKE is a key mediator of Ras activation of NF-κB and Ras oncogenic function

Abstract

Abstract Accumulating evidence indicates that the NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. IKBKE has been shown to activate NF-κB through both canonical and non-canonical pathways. Here we show that activating mutations of Ras significantly induce IKBKE kinase activity and that depletion of KRas results in decrease of IKBKE activity only in KRAS mutant but wild-type cells. KRas-induced NF-κB DNA-binding and transcription activity was abrogated by knockdown of IKBKE. In addition, we demonstrated significant decrease of lung tumor development in Ikbke-/-;KRasLA1 mice when compared to Ikbke+/-;KRasLA1 and Ikbke+/+;KRasLA1 animals. Furthermore, depletion of IKBKE selectively reduces cell survival and tumor growth in K-Ras mutant non-small cell lung cancer cells. These data identify IKBKE as a downstream effector of Ras which mediates RAS activation of NF-κB and Ras tumorigenic activity. Citation Format: Donghwa Kim, Jianping Guo, Sridevi Challa, Domenico Coppola, Jin Q. Cheng. IKBKE is a key mediator of Ras activation of NF-κB and Ras oncogenic function. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4416. doi:10.1158/1538-7445.AM2014-4416