Journal
CANCER CELL
Volume 25, Issue 5, Pages 638-651Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2014.03.017
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Funding
- Cancer Target Discovery and Development Centers NCI [U01 CA168426]
- Michigan Center for Translational Pathology, SPORE [P50 CA69568]
- V-Foundation for Cancer Research
- Marie Curie International Outgoing Fellowship [PIOF-GA-2009-253290]
- Catalan Institute of Oncology-Bellvitge Institute for Biomedical Research, Barcelona, Spain
- Prostate Cancer Foundation
- [CA084294]
- [U54 CA121852]
- [CA154293]
- [DK076602]
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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.
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