Cross-species Regulatory Network Analysis Identifies a Synergistic Interaction Between FOXM1 and CENPF That Drives Prostate Cancer Malignancy

Cancer Cell. 2014 May 12;25(5):638-651. doi: 10.1016/j.ccr.2014.03.017.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone / genetics*
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Gene Silencing
  • Humans
  • Male
  • Mice
  • Microfilament Proteins / genetics*
  • Models, Biological
  • Neoplasm Metastasis
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Signal Transduction / genetics
  • Transcription, Genetic

Substances

  • Chromosomal Proteins, Non-Histone
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Microfilament Proteins
  • centromere protein F

Associated data

  • GEO/GSE53202