LMO4 can interact with Smad proteins and modulate transforming growth factor-β signaling in epithelial cells

Z. Lu, Kit Lam, N. Wang, X. Xu, M. Cortes, B. Andersen

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

LIM-only protein 4 (LMO4) plays critical roles in mammalian development, and has been proposed to play roles in epithelial oncogenesis, including breast cancer. As LMO4 is highly expressed in the epithelial compartments at locations of active mesenchymal-epithelial interactions, we reasoned that LMO4 might act by modulating signaling pathways involved in mesenchymal-epithelial signaling. One such candidate signal is the transforming growth factor-β (TGFβ) cytokine pathway, which plays important roles both in development and cancer. We show here that the transcriptional response to TGFβ in epithelial cells is sensitive to LMO4 levels; both up- and downregulation of LMO4 can enhance TGFβ signaling as assessed by a TGFβ-responsive reporter gene. Furthermore, LMO4 can interact with the MH1 and linker domains of receptor-mediated Smad proteins, and associate with the endogenous TGFβ-responsive Plasminogen Activator Inhibitor-1 gene promoter in a TGFβ-dependent manner, suggesting that such interactions may mediate the effects of LMO4 on TGFβ signaling. When introduced into mammary epithelial cells, LMO4 potentiated the growth-inhibitory effects of TGFβ in those cells. These results define a new function for LMO4 as a coactivator in TGFβ signaling, and provide a potential novel mechanism for LMO4-mediated regulation in development and oncogenesis.

Original languageEnglish (US)
Pages (from-to)2920-2930
Number of pages11
JournalOncogene
Volume25
Issue number20
DOIs
StatePublished - May 11 2006

Fingerprint

Smad Proteins
Transforming Growth Factors
Epithelial Cells
Proteins
Carcinogenesis
Plasminogen Activator Inhibitor 1
Reporter Genes
Breast
Up-Regulation
Down-Regulation

Keywords

  • Cellular proliferation
  • LMO4
  • Mammary gland epithelial cells
  • Smads
  • Transforming growth factorβ

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

LMO4 can interact with Smad proteins and modulate transforming growth factor-β signaling in epithelial cells. / Lu, Z.; Lam, Kit; Wang, N.; Xu, X.; Cortes, M.; Andersen, B.

In: Oncogene, Vol. 25, No. 20, 11.05.2006, p. 2920-2930.

Research output: Contribution to journalArticle

Lu, Z. ; Lam, Kit ; Wang, N. ; Xu, X. ; Cortes, M. ; Andersen, B. / LMO4 can interact with Smad proteins and modulate transforming growth factor-β signaling in epithelial cells. In: Oncogene. 2006 ; Vol. 25, No. 20. pp. 2920-2930.
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