Oncogenic targeting of BRM drives malignancy through C/EBPβ-dependent induction of α5 integrin.

ABSTRACT: Integrin expression and activity are altered in tumors, and aberrant integrin signaling promotes malignancy. However, how integrins become altered in tumors remains poorly understood. We discovered that oncogenic activation of MEK signaling induces cell growth and survival, and promotes the malignant phenotype of mammary epithelial cells (MECs) by increasing α5 integrin expression. We determined that MEK activates c-Myc to reduce the transcription of the SWI/SNF chromatin remodeling enzyme Brahma (BRM). Our studies revealed that reduced BRM expression and/or activity drives the malignant behavior of MECs by epigenetically promoting C/EBPβ expression to directly induce α5 integrin transcription. Consistently, we could show that restoring BRM levels normalized the malignant behavior of trans

SUBMITTER: Damiano L 

PROVIDER: S-EPMC3960370 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature