An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes

PLoS Genet. 2016 Apr 13;12(4):e1005989. doi: 10.1371/journal.pgen.1005989. eCollection 2016 Apr.

Abstract

Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / genetics
  • Lung Neoplasms / secondary*
  • Mammary Neoplasms, Animal / diagnosis
  • Mammary Neoplasms, Animal / genetics*
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Inbred NZB
  • Mice, Transgenic
  • Nectins
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rosiglitazone
  • Thiazolidinediones / pharmacology

Substances

  • Cell Adhesion Molecules
  • Kruppel-Like Transcription Factors
  • Nectins
  • Promyelocytic Leukemia Zinc Finger Protein
  • RNA, Small Interfering
  • Thiazolidinediones
  • Zbtb16 protein, mouse
  • Rosiglitazone