Abstract A39: BACH1 and RKIP participate in a bistable network that affects progression to metastasis in breast Cancer

Abstract

Abstract The sources of nongenetic variability in metastatic progression are largely unknown. To address this question, we characterized a transcriptional regulatory network for the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP). We previously showed that the transcription factor BACH1 is negatively regulated by RKIP, promotes breast cancer metastasis, and negatively correlates with RKIP expression in primary breast tumors. Here we demonstrate that BACH1 acts in a double negative (overall positive) feedback loop to inhibit RKIP transcription in breast cancer cells. BACH1 also negatively regulates its own transcription. HDAC inhibitors increased BACH1 but not RKIP transcription, whereas depletion of polycomb repressor EZH2 induced RKIP transcription. Analysis of the BACH1 network reveals the existence of a bistable, inverse relationship between BACH1 and RKIP that can potentially give rise to nongenetic variability. Together, our results suggest that the balance between RKIP and BACH1 plays a key role in determining metastatic progression in breast cancers. Citation Format: Jiyoung Lee, Jieun Yun, Kam Yeung, Elena Bevilacqua, Gábor Balázsi, Marsha Rich Rosner. BACH1 and RKIP participate in a bistable network that affects progression to metastasis in breast Cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A39.