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

Overview

MeSH Major

  • Chromosomal Proteins, Non-Histone
  • Forkhead Transcription Factors
  • Gene Regulatory Networks
  • Microfilament Proteins
  • Prostatic Neoplasms

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 date

  • May 12, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4051317

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2014.03.017

PubMed ID

  • 24823640

Additional Document Info

start page

  • 638

end page

  • 51

volume

  • 25

number

  • 5