The RON receptor tyrosine kinase: A key regulator of inflammation and cancer progression

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Abstract

Numerous studies have documented abnormal expression and activation of the Ron receptor tyro-sine kinase in a variety of human malignancies. Here we review the literature regarding the molecular mechanisms governing Ron regulation, the biological functions of Ron, the effect of Ron on cancer development, and potential therapeutic implications. In epithelial cells, activation of Ron by its ligand, macrophage stimulating protein, mediates a number of biological events including cell growth, motility, and epithelial to mesenchymal transition. Overexpression and/or activation of Ron has been implicated in the progression and metastasis of diverse epithelial cancers, where it plays a causal role in tumor development by promoting growth, survival, and motility of tumor cells. As a crucial regulator of inflammation, Ron inhibits classic macrophage activation and promotes alternative activation of macrophages, resulting in the resolution of inflammation and tissue repair. In addition, Ron alleviates antitumor immunity by promoting the alternative activation of tumor-associated macrophages, and Ron expression in the tumor microenvironment promotes the outgrowth of metastatic colonies. Hence, Ron is a promising therapeutic target for the treatment of epithelial cancers.

Original languageEnglish (US)
Pages (from-to)549-574
Number of pages26
JournalCritical Reviews in Immunology
Volume33
Issue number6
DOIs
StatePublished - Oct 15 2013

All Science Journal Classification (ASJC) codes

  • Immunology

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