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Updated: May 28, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells

Sangmin Kim1, Jeonghun Han, Se Kyung Lee

  • 1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.

Cancer Letters
|October 29, 2011
PubMed

Insights

Smad7 inhibits both TGF-β1 and EGF signaling pathways in breast cancer cells. Overexpression of Smad7 blocks EGF-induced MMP-9 expression by inhibiting smad3 phosphorylation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • The role of Smad7 in the Epidermal Growth Factor (EGF) signaling pathway is not fully understood.
  • Smad7 is known to inhibit the Transforming Growth Factor-beta (TGF-β) signaling pathway.

Purpose of the Study:

  • To investigate the effect of Smad7 on EGF-induced Matrix Metalloproteinase-9 (MMP-9) expression in SKBR3 breast cancer cells.
  • To elucidate the inhibitory mechanisms of Smad7 in both EGF and TGF-β signaling.

Main Methods:

  • Utilized EGF and TGF-β1 treatments, EGFR inhibitor (AG1478), MEK1/2 inhibitor (UO126), JNK inhibitor (SP600125), and smad3 inhibitor (SIS3).
  • Employed Smad7 overexpression (including adenoviral delivery - Ad-smad7) and smad3 siRNA transfection.
  • Assessed phosphorylation of EGFR, smad3, ERK, and JNK, alongside MMP-9 expression levels.

Main Results:

  • EGF and TGF-β1 co-treatment increased Smad7 and MMP-9 expression.
  • EGF induced phosphorylation of EGFR, smad3, ERK, and JNK, leading to MMP-9 expression, which was blocked by AG1478, UO126, and SIS3, but not SP600125.
  • Smad7 overexpression inhibited EGF-induced smad3 phosphorylation and MMP-9 expression, as well as basal MMP-9 expression induced by EGF or TGF-β1.

Conclusions:

  • EGF-induced MMP-9 expression is mediated by smad3 phosphorylation.
  • Smad7 acts as an inhibitor of both the TGF-β1 and EGF signaling pathways in SKBR3 breast cancer cells.
  • Smad7's inhibitory effect on EGF signaling involves the suppression of smad3 phosphorylation.

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