Quantitative proteomic analysis identifies new effectors of FOXM1 involved in breast cancer cell migration

Int J Clin Exp Pathol. 2015 Dec 1;8(12):15836-44. eCollection 2015.

Abstract

The Forkhead Box M1 (FOXM1) transcription factor plays important roles in tumorigenesis and tumor metastasis in multiple human carcinomas. However, the underlying mechanisms for FOXM1 function remain to be classified. In the present study, we employed quantitative proteomic approach to search new downstream targets of FOXM1 in breast cancer MDA-MB-231 cells. A total of 4125 proteins were identified and quantified by label-free quantitation, of which 318 proteins were significantly changed (with P-value <0.05) between FOXM1 knockdown cells and control cells. Among them, three proteins ACSL4, CGGBP1 and PGRMC2 were significantly downregulated with FOXM1 reduction by western blot analysis. Further functional assays revealed that knockdown of the three proteins in MDA-MB-231 cells attenuated the ability of cell migration, consistent with the phenotype of FOXM1 knockdown. These results suggest that new potential downstream effectors of FOXM1 were identified by proteomic approach, and may provide new potential therapeutic targets in breast cancer.

Keywords: FOXM1; breast cancer; cell migration; quantitative proteomic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Phenotype
  • Proteomics / methods*
  • RNA Interference
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Reproducibility of Results
  • Signal Transduction
  • Tandem Mass Spectrometry
  • Transfection

Substances

  • Biomarkers, Tumor
  • CGGBP1 protein, human
  • DNA-Binding Proteins
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Membrane Proteins
  • PGRMC2 protein, human
  • Receptors, Progesterone
  • Coenzyme A Ligases
  • long-chain-fatty-acid-CoA ligase