Mechanisms of RON-mediated epithelial-mesenchymal transition in MDCK cells through the MAPK pathway

Xu Xiangming1, Qian Yun, Zhang Guoliang

  • 1Colorectal Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Xuxiangming1974@msn.com

Insights

The RON protein mediates epithelial-mesenchymal transition (EMT) in kidney cells. Macrophage stimulating protein (MSP) activates RON, triggering cell migration and EMT markers via the Erk1/2 pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial-mesenchymal transition (EMT) is crucial for neoplastic metastasis.
  • The role of the RON protein in EMT processes requires further elucidation.

Purpose of the Study:

  • To investigate the role and mechanisms of RON protein in mediating EMT in Madin-Darby canine kidney (MDCK) cells.
  • To identify the signaling pathways involved in RON-induced EMT.

Main Methods:

  • Western blot analysis to assess protein expression.
  • Cell migration assays to quantify cell movement.
  • Transfection of MDCK cells with wt-RON cDNA.
  • Pharmacological inhibition of specific signaling pathways (MAPK/ERK kinase inhibitor PD98059).

Main Results:

  • Macrophage stimulating protein (MSP) activation of RON induced cell migration and morphological changes in transfected MDCK cells.
  • RE7 cells (MDCK cells transfected with wt-RON) exhibited decreased E-cadherin and increased vimentin and Snail expression compared to control MDCK cells.
  • MSP stimulation of RE7 cells led to increased migration and activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and glycogen synthase kinase-3β (GSK-3β).
  • Inhibition of MAPK/ERK kinase significantly reduced MSP-induced migration and signaling pathway activation.

Conclusions:

  • RON protein mediates EMT in MDCK cells, primarily through the Erk1/2 signaling pathway.
  • GSK-3β plays a regulatory role in controlling Snail function and EMT progression via this pathway.

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