Summary To identify regulatory drivers of prostate cancer malignancy, we have assembled genome-wide regulatory networks (interactomes) for human and mouse prostate cancer from expression profiles of human tumors and of genetically engineered mouse models, respectively. Cross-species computational analysis of these interactomes has identified FOXM1 and CENPF as synergistic master regulators of prostate cancer malignancy. Experimental validation shows that FOXM1 and CENPF function synergistically to promote tumor growth, by coordinated regulation of target gene expression and activation of key signaling pathways associated with prostate cancer malignancy. Furthermore, co-expression of FOXM1 and CENPF is a robust prognostic indicator of poor survival and metastasis. Thus, genome-wide cross-species interrogation of regulatory networks represents a valuable strategy to identify causal mechanisms of human cancer.

The authors wish to note, "The colony formation assay for SNU-1 upon enoxacin treatment in Fig. 1B is incorrect because of inadvertent duplication with the SNU-638 sample during the preparation of the figure. We have now replaced it with the correct assay. The data for RKO.shTRBP in Fig. 3C were erroneously graphed because the mean fold change was derived from an incorrect Fig. S5A where the formula used for quantitative RT-PCR analysis was ΔctAssay/ΔctControl rather than the correct formula 2-(ΔctAssay-ΔctControl). The data for RKO.shTRBP in Fig. S5A and CRC56 and CRC43 in Fig. S9B were erroneously graphed because of the same error with the formula. The corrected figures and their legends appear below. The figures in the supplemental information have also been corrected. These errors do not affect the conclusions of the article. We sincerely regret these mistakes. The error bars on the graphs used throughout the article indicate standard deviation (SD)."The corrected Fig. 1, Fig. 3, Fig. S5, and Fig. S9 appear below, along with their corresponding legends. The SI has been corrected online.