Cross-Species Regulatory Network Analysis Identifies a Synergistic Interaction between FOXM1 and CENPF that Drives Prostate Cancer Malignancy

Alvaro Aytes, Antonina Mitrofanova, Celine Lefebvre, Mariano J. Alvarez, Mireia Castillo-Martin, Tian Zheng, James A. Eastham, Anuradha Gopalan, Kenneth J. Pienta, Michael M. Shen, Andrea Califano, Cory Abate-Shen

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)638-651
Number of pages14
JournalCancer cell
Volume25
Issue number5
DOIs
StatePublished - May 12 2014

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Aytes, A., Mitrofanova, A., Lefebvre, C., Alvarez, M. J., Castillo-Martin, M., Zheng, T., Eastham, J. A., Gopalan, A., Pienta, K. J., Shen, M. M., Califano, A., & Abate-Shen, C. (2014). Cross-Species Regulatory Network Analysis Identifies a Synergistic Interaction between FOXM1 and CENPF that Drives Prostate Cancer Malignancy. Cancer cell, 25(5), 638-651. https://doi.org/10.1016/j.ccr.2014.03.017