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Review
. 2007 Aug;3(4):441-8.
doi: 10.2217/14796694.3.4.441.

Ron-receptor tyrosine kinase in tumorigenesis and metastasis

Mike A Leonis  1 , Megan N Thobe, Susan E Waltz
Affiliations
Review

Ron-receptor tyrosine kinase in tumorigenesis and metastasis

Mike A Leonis et al. Future Oncol. 2007 Aug.

Abstract

The Ron-receptor tyrosine kinase has been increasingly recognized for its tumorigenic potential in the last decade. Ron-receptor activation leads to the activation of common receptor tyrosine kinase downstream-signaling pathways, and most prominently in tumor models, activation of MAPK, PI3K and beta-catenin. Numerous experimental models of mammalian tumorigenesis have demonstrated that increased Ron-receptor activity correlates with increased tumorigenesis in a variety of organs of epithelial origin. The evidence for Ron as an oncogene in human tumor biology is growing. The Ron receptor is overexpressed and over activated in a large number of human tumors, and overexpression of Ron correlates with a worse clinical outcome for patients in at least two human cancer states, namely breast and bladder cancer. Several experimental approaches have been demonstrated to successfully block Ron activity and function, and given these convincing data, approaches to block Ron-receptor activity in targeted human cancers should prove to be fruitful in the setting of future clinical research trials.

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References

    1. Camp ER, Yang A, Gray MJ, et al. Tyrosine kinase receptor RON in human pancreatic cancer: expression, function, and validation as a target. Cancer. 2007;109(6):1030–1039. - PubMed
    1. Cheng HL, Liu HS, Lin YJ, et al. Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer. 2005;92(10):1906–1914. - PMC - PubMed
    1. Hsu PY, Liu HS, Cheng HL, et al. Collaboration of RON and epidermal growth factor receptor in human bladder carcinogenesis. J Urol. 2006;176(5):2262–2267. - PubMed

    1. Lee WY, Chen HH, Chow NH, et al. Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients. Clin Cancer Res. 2005;11(6):2222–2228. **The data in this paper reports the expression of Ron in node negative breast cancers and documents the significance of this receptor with prognosis.

    1. O'Toole JM, Rabenau KE, Burns K, et al. Therapeutic implications of a human neutralizing antibody to the macrophage-stimulating protein receptor tyrosine kinase (RON), a c-MET family member. Cancer Res. 2006;66(18):9162–9170. *This report documents the overexpression of Ron in an extensive panel of human tumor types and cell lines and also documents benefit for a blockade of Ron receptor function in tumor xenographs.

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