Abstract IA5: Using cross-species analysis of genome-wide regulatory networks to identify drivers of cancer malignancy

Abstract

Abstract We have been interested in using systems biology approaches for cross-species interrogations of cancer phenotypes. To identify regulatory drivers of prostate cancer malignancy, we have performed cross-species analysis of complementary human and mouse gene regulatory networks (interactomes) assembled from molecular profiles of human tumors and genetically engineered prostate cancer mouse models, respectively. Genome-wide analysis of these interactomes reveals extensive conservation of their transcriptional programs, particularly those known to be essential for prostate tumorigenesis. Cross-species interactome interrogation and subsequent experimental validation have elucidated a synergistic interaction of FOXM1 and CENPF that drives prostate cancer malignancy. Silencing of both FOXM1 and CENPF, but not either individually, abrogates prostate tumor growth in vivo via cooperative regulation of key signaling pathways in prostate cancer progression. Furthermore, co-expression of FOXM1 and CENPF is a highly robust prognostic indicator of disease outcome. Taken together, these analyses suggest that genome-wide cross-species interrogation of regulatory networks represents a valuable new strategy to identify causal mechanisms of human cancer. Citation Format: Cory Abate-Shen. Using cross-species analysis of genome-wide regulatory networks to identify drivers of cancer malignancy. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr IA5.