TGF-Β1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells

S. B. Pakala, K. Singh, S. D.N. Reddy, K. Ohshiro, D. Q. Li, L. Mishra, R. Kumar

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2230-2241
Number of pages12
JournalOncogene
Volume30
Issue number19
DOIs
StatePublished - May 12 2011
Externally publishedYes

Keywords

  • epithelial-to-mesenchymal transition
  • FosB
  • MTA1
  • target gene transcription
  • TGF-β1 signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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