TGF-β1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells

Oncogene. 2011 May 12;30(19):2230-41. doi: 10.1038/onc.2010.608. Epub 2011 Jan 24.

Abstract

In spite of a large number of transforming growth factor β1 (TGF-β1)-regulated genes, the nature of its targets with roles in transformation continues to be poorly understood. Here, we discovered that TGF-β1 stimulates transcription of metastasis-associated protein 1 (MTA1), a dual master coregulator, in epithelial cells, and that MTA1 status is a determinant of TGF-β1-induced epithelial-to-mesenchymal transition (EMT) phenotypes. In addition, we found that MTA1/polymerase II/activator protein-1 (AP-1) co-activator complex interacts with the FosB-gene chromatin and stimulates its transcription, and FosB in turn, utilizes FosB/histone deacetylase 2 complex to repress E-cadherin expression in TGF-β1-stimulated mammary epithelial cells. These findings suggest that TGF-β1 regulates the components of EMT via stimulating the expression of MTA1, which in turn, induces FosB to repress E-cadherin expression and thus, revealed an inherent function of MTA1 as a target and effector of TGF-β1 signaling in epithelial cells.

Publication types

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

MeSH terms

  • Animals
  • Chromatin Immunoprecipitation
  • Electrophoretic Mobility Shift Assay
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Histone Deacetylases / metabolism*
  • Humans
  • Mice
  • Microscopy, Confocal
  • Polymerase Chain Reaction
  • Protein Binding
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Repressor Proteins / metabolism*
  • Signal Transduction*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • FOSB protein, human
  • Mta1 protein, human
  • Proto-Oncogene Proteins c-fos
  • Repressor Proteins
  • Transforming Growth Factor beta1
  • Histone Deacetylases