Abstract 1955: IKKϵ maintains MEK activation and suppresses non-canonical NF-κB signaling in triple-negative breast cancer

Abstract

Abstract Metastatic breast cancer carries a poor prognosis despite the success of newly targeted therapies. Treatment options remain especially limited for the subtype of triple negative breast cancer (TNBC). Several signaling pathways, including NF-κB, are altered in TNBC, and the complexity of this disease implies multifaceted pathway interactions and compensatory signaling. We hypothesized that a subset of TNBCs expresses IKKϵ to promote a specific NF-κB signaling program that can enhance metastatic potential. Our data suggest that IKKϵ supports MEK activation and suppresses non-canonical signaling by the p52 NF-κB transcription factor. We found that NF-κB p52 expression is inversely proportional to activated MEK. We further demonstrate that IKKϵ and MEK cooperate to support viability and invasion potential under adherent conditions, whereas the p52 transcription factor supports viability under non-adherent conditions, underscoring the contrasting roles of these proteins. This study illustrates the diverse roles of NF-κB signaling components in TNBC, and highlights the adaptability of NF-κB in maintaining cancer cell survival under different microenvironments. A better understanding of the diversity of NF-κB signaling may ultimately improve the development of novel therapeutic regimens for TNBC. Citation Format: Carrie House, Valentina Grajales, Helmae Wubneh, Danielle Kimble, Marianne Kim, Christina Annunziata. IKKϵ maintains MEK activation and suppresses non-canonical NF-κB signaling in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1955. doi:10.1158/1538-7445.AM2015-1955