The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness

Piera Maggiora1, Annalisa Lorenzato, Stefano Fracchioli

  • 1Laboratory of Cancer Genetics of the Institute for Cancer Research and Treatment, University of Torino School of Medicine, SP 142, Km 3.95, 10060 Candiolo (Torino), Italy.

Insights

Ovarian cancer cells expressing both RON and MET receptors show increased motility and invasiveness. Simultaneous ligand stimulation significantly enhances invasion, suggesting co-receptor expression promotes ovarian cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The receptor tyrosine kinase (RTK) family includes MET, linked to human tumorigenesis.
  • RON and MET receptors are known to interact and synergize in signaling pathways.

Purpose of the Study:

  • To investigate the expression and functional significance of RON and MET co-expression in human ovarian carcinomas.
  • To determine the role of RON and MET signaling in ovarian cancer cell motility and invasiveness.

Main Methods:

  • Analysis of RON and MET expression in human ovarian carcinoma samples and cell lines.
  • Assessment of ovarian cancer cell motility and invasiveness in response to ligands MSP and HGF.
  • Evaluation of invasion through basement membrane and collagen gel models.

Main Results:

  • RON and MET were coexpressed in 42% of human ovarian carcinomas.
  • No mutations were found in the kinase domains of RON and MET.
  • Ovarian cancer cells coexpressing MET and RON showed increased motility and invasiveness elicited by HGF and MSP.
  • Simultaneous addition of HGF and MSP significantly enhanced invasion.

Conclusions:

  • Coexpression of MET and RON receptors provides a selective advantage to ovarian cancer cells.
  • The MET-RON signaling axis may play a critical role in promoting ovarian cancer progression and metastasis.

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