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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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CD147-induced cell proliferation is associated with Smad4 signal inhibition

Hui Qin1, Azhar Rasul2, Xin Li1

  • 1The Key Laboratory of Molecular Epigenetic, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, PR China.

Experimental Cell Research
|July 8, 2017
PubMed

Insights

CD147 promotes cancer cell proliferation by inhibiting the Smad4/p21 pathway. This interaction involves CD147 binding to Smad4, impacting its nuclear transport and downstream signaling, offering a new therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • CD147 (basigin) is a transmembrane glycoprotein overexpressed in various cancers.
  • The precise mechanisms by which CD147 influences cancer cell proliferation remain incompletely elucidated.
  • Understanding CD147's role is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of CD147 in modulating prostate cancer cell proliferation.
  • To explore the association between CD147 and the transforming growth factor-beta (TGF-β)/Smad4 signaling pathway.
  • To identify the molecular interactions underlying CD147's function in cell growth.

Main Methods:

  • Cell viability and clone formation assays in LNCaP prostate cancer cells.
  • Luciferase and Western blot analyses to assess gene expression changes.
  • Immunofluorescence, nuclear-cytoplasmic separation, GST pull-down, and co-immunoprecipitation assays to study protein interactions.
  • Site-directed mutagenesis to investigate specific phosphorylation sites.

Main Results:

  • CD147 significantly promotes cell proliferation in prostate cancer models.
  • Silencing CD147 upregulates the expression of p21WAF1, a cell cycle inhibitor.
  • CD147 directly interacts with Smad4, facilitating its nuclear translocation and inhibiting the Smad4/p21WAF1 signaling axis.
  • Phosphorylation at serine 252 (pSer252) of CD147 is critical for Smad4 binding and subsequent inhibition of proliferation.

Conclusions:

  • CD147 promotes cancer cell proliferation by inhibiting the Smad4/p21WAF1 pathway.
  • Smad4 is identified as a novel binding partner of CD147, with the interaction mediated by CD147-ICD and Smad4 MH2 domains.
  • The pSer252 site on CD147 plays a key role in regulating this interaction and influencing cell growth, presenting a potential therapeutic target.
Keywords:
CD147CancerSmad4p21(WAF1)

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