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Histone demethylase RBP2 promotes malignant progression of gastric cancer through

Xiuming Liang1, Jiping Zeng2, Lixiang Wang3

  • 1Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.

Oncotarget
|May 15, 2015
PubMed

Insights

The histone demethylase RBP2 drives gastric cancer (GC) metastasis by suppressing E-cadherin. Targeting RBP2 may inhibit tumor progression and prevent metastasis.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Feedback pathways are crucial in tumor development and malignant progression.
  • Epigenetic regulation mechanisms in these pathways remain unclear.

Purpose of the Study:

  • To elucidate the role of the histone demethylase RBP2 in gastric cancer (GC) metastasis.
  • To investigate the TGF-β1-(p-Smad3)-RBP2-E-cadherin-Smad3 feedback circuit in GC progression.

Main Methods:

  • In vitro and in vivo studies involving RBP2 knockdown in GC cells.
  • Analysis of RBP2 binding to the E-cadherin promoter.
  • Investigation of TGF-β1 and p-Smad3 pathway involvement.

Main Results:

  • RBP2 knockdown significantly inhibited GC cell metastasis.
  • RBP2 directly suppresses E-cadherin expression by binding to its promoter, facilitating epithelial-mesenchymal transition (EMT) and metastasis.
  • TGF-β1 induces RBP2 via the p-Smad3 pathway, creating a positive feedback loop that enhances GC metastasis.

Conclusions:

  • A novel TGF-β1-(p-Smad3)-RBP2-E-cadherin-Smad3 feedback circuit promotes GC malignant progression and metastasis.
  • RBP2 suppression represents a potential therapeutic strategy to prevent tumor distant metastasis.
Keywords:
RBP2TGF-β1feedback circuitmetastasis

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