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Updated: Mar 2, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Inhibition of ERK1/2 Signaling Impairs the Promoting Effects of TGF-β1 on Hepatocellular Carcinoma Cell Invasion and

Ling Liu, Nianfeng Li, Qi Zhang

    Oncology Research
    |May 12, 2017
    PubMed

    Insights

    Transforming growth factor-β (TGF-β) activates ERK1/2 signaling in liver cancer cells via Smad2/3, promoting metastasis. Inhibiting ERK1/2 reduces TGF-β-driven invasion without impacting proliferation, suggesting ERK1/2 as a therapeutic target.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cell Signaling

    Background:

    • Transforming growth factor-β (TGF-β) and ERK signaling are implicated in human cancers, including hepatocellular carcinoma (HCC).
    • The precise mechanisms by which TGF-β influences HCC progression, particularly its dual roles in promoting and suppressing tumor growth, remain incompletely understood.
    • Understanding these pathways is crucial for developing targeted therapies for HCC.

    Purpose of the Study:

    • To investigate the role of ERK1/2 signaling in mediating the effects of TGF-β on hepatocellular carcinoma (HCC) cells.
    • To elucidate the specific pathways involved in TGF-β-induced invasion and proliferation in HCC.
    • To identify potential molecular targets for treating TGF-β-responsive HCC.

    Main Methods:

    • Utilized HCC HepG2 cells treated with TGF-β1, TGF-β inhibitor (SB431542), and MEK1/2 inhibitor (U0126).
    • Assessed cell invasion, epithelial-mesenchymal transition (EMT) markers (vimentin), MMP9 production and activation, and cell proliferation.
    • Investigated the involvement of Smad2/3 and Slug pathways through gene expression inhibition and phosphorylation analysis.

    Main Results:

    • TGF-β1 treatment enhanced invasion, EMT, and MMP9 activity in HepG2 cells, while inhibiting proliferation.
    • MEK1/2 inhibition (U0126) reduced TGF-β1-induced invasion and MMP9 secretion but did not affect proliferation inhibition.
    • Smad2/3 pathway activation was necessary for TGF-β1-induced invasion, ERK1/2 phosphorylation, and MMP9 production, whereas Slug played a lesser role in invasion.

    Conclusions:

    • TGF-β1 activates ERK1/2 signaling in HCC cells predominantly through the Smad2/3 pathway.
    • Inhibition of ERK1/2 signaling effectively attenuates the pro-metastatic effects of TGF-β1 in HCC without compromising its anti-proliferative activity.
    • Targeting ERK1/2 signaling represents a promising therapeutic strategy for managing TGF-β-responsive hepatocellular carcinoma.

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