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MDM2 promotes epithelial-mesenchymal transition through activation of Smad2/3 signaling pathway in lung

Yong Tang1,2, Yiwen Xuan2, Guibin Qiao3

  • 1Southern Medical University, Guangzhou, China, yingl1952@163.com.

Oncotargets and Therapy
|April 17, 2019
PubMed
Abstract

Insights

Mouse double minute 2 (MDM2) promotes lung adenocarcinoma (LAC) metastasis and epithelial-mesenchymal transition (EMT) by activating the Smad2/3 pathway. Inhibiting MDM2 suppressed tumor growth and EMT progression in vivo and in vitro.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Mouse double minute 2 (MDM2) is implicated in cancer metastasis and epithelial-mesenchymal transition (EMT).
  • Lung adenocarcinoma (LAC) is a significant cause of cancer-related mortality.
  • Understanding the molecular mechanisms driving LAC progression is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of MDM2 in mediating EMT in LAC.
  • To explore the involvement of the small mothers against decapentaplegic (Smad) signaling pathway in MDM2-induced EMT.
  • To evaluate the therapeutic potential of targeting MDM2 in LAC.

Main Methods:

  • MDM2 expression was analyzed in LAC tissues and cell lines.
  • MDM2 was overexpressed in PC9 cells and silenced in H1975 cells.
  • Smad2 and Smad3 were silenced using siRNA to investigate pathway involvement.
  • In vivo studies were conducted using nude mice to assess MDM2's effect on tumor growth.

Main Results:

  • MDM2 was significantly upregulated in LAC tissues and certain cell lines.
  • MDM2 overexpression enhanced proliferation, migration, invasion, and inhibited apoptosis in LAC cells.
  • MDM2 silencing reduced EMT markers (N-cadherin, vimentin) and increased epithelial markers (E-cadherin, β-catenin).
  • MDM2 knockdown inhibited tumor growth in vivo.
  • Smad2/3 pathway activation was correlated with MDM2 expression and EMT progression.

Conclusions:

  • MDM2 plays a critical role in promoting proliferation and EMT in LAC.
  • MDM2 activates the Smad2/3 signaling pathway, driving LAC progression.
  • Targeting MDM2 may represent a potential therapeutic strategy for LAC.
Keywords:
MDM2Smad signaling pathwaycell metastasisepithelial–mesenchymal transitionlung adenocarcinoma

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