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Oncogenic signaling pathways activated by RON receptor tyrosine kinase

Alla Danilkovitch-Miagkova1

  • 1Department of Immunochemistry, PPD Development, 2244 Dabney Road, Richmond, VA 23230, USA. Alla.Danilkovitch@richmond.ppdi.com

Current Cancer Drug Targets
|February 7, 2003
PubMed

Insights

The RON receptor tyrosine kinase and its ligand MSP regulate normal cell functions. Aberrant RON signaling is implicated in cancer development and metastasis through activation of key oncogenic pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The MET receptor tyrosine kinase family includes RON, expressed in macrophages, epithelial, and hematopoietic cells.
  • Macrophage stimulating protein (MSP) is the ligand for RON, regulating cell growth, survival, adhesion, motility, cytokine production, and phagocytosis.
  • RON plays a role in normal cellular functions and is increasingly recognized for its involvement in cancer.

Purpose of the Study:

  • To review the signaling pathways activated by RON.
  • To elucidate the role of RON in oncogenic cell transformation and tumor progression.
  • To highlight the potential involvement of RON in tumor metastasis.

Main Methods:

  • Literature review of accumulated data on RON function and signaling.
  • Analysis of experimental evidence linking RON mutations to oncogenic transformation.
  • Examination of RON expression and activity in primary tumors and cell lines.

Main Results:

  • RON is overexpressed and constitutively active in certain tumors and cell lines.
  • Experimental mutations in RON lead to oncogenic cell transformation.
  • RON activation is linked to susceptibility to virus-induced erythroleukemia in mice.
  • Constitutive activation of pathways like PI-3K/AKT, beta-catenin, MAPK, and JNK underlies RON-mediated transformation.

Conclusions:

  • RON-activated signaling pathways are crucial for normal cellular processes.
  • Dysregulated RON signaling contributes significantly to cancer development and progression.
  • Understanding RON pathways offers potential therapeutic targets for cancer treatment and metastasis inhibition.

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