FOXM1 promotes the epithelial to mesenchymal transition by stimulating the transcription of Slug in human breast cancer

Cancer Lett. 2013 Oct 28;340(1):104-12. doi: 10.1016/j.canlet.2013.07.004. Epub 2013 Jul 12.

Abstract

The Forkhead Box M1 (FOXM1) transcription factor is involved in tumorigenesis and tumor progression in multiple human carcinomas. In this study, we found that FOXM1 promoted the epithelial to mesenchymal transition (EMT) in human breast cancer. We observed a strong correlation between the expression levels of FOXM1 and the mesenchymal phenotype. Knockdown of FOXM1 inhibited the mesenchymal phenotype, whereas stable overexpression of FOXM1 induced EMT in breast cancer cells. FOXM1 was found to endogenously bind to and stimulate the promoter of Slug that is crucial for EMT progression. The knockdown of Slug abolished the EMT-inducing function of FOXM1. The stable overexpression of FOXM1 promoted metastasis of breast cancer cells in vivo. This study confirmed that FOXM1 promoted EMT in breast cancer cells by stimulating the transcription of EMT-related genes such as Slug.

Keywords: Breast cancer; EMT; FOXM1 transcription factor; Slug Transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Female
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / physiology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / secondary*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplastic Cells, Circulating / metabolism
  • Snail Family Transcription Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transcriptional Activation

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • SNAI1 protein, human
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors