Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

Chan, Edward L.; Peace, Belinda E.; Collins, Margaret H.; Toney-Earley, Kenya; Waltz, Susan E.

doi:10.1038/sj.onc.1208231

Cited by 26 publications

(23 citation statements)

References 35 publications

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“…These TK regulate very diverse biological responses, including proliferation, motility, invasiveness, and cellular dissociation. When a kinase domain-deficient Ron receptor was crossed onto Tg.AC, TPA-induced papillomas were found to be smaller in volume and less likely to convert to malignancy (Chan et al, 2005).…”

Section: Pathway Interactionsmentioning

confidence: 99%

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

et al. 2005

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Section: Pathway Interactionsmentioning

confidence: 99%

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

et al. 2005

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“…In addition, tumors from the Ron-deficient mice exhibited less cellular proliferation and microvessel density compared to controls and had an increase in the amount of apoptotic cells. In the second model, the impact of Ron signaling was analyzed in a Ras-mediated model of chemically-induced skin carcinogenesis [48]. In this model, there were a greater number of benign skin papillomas produced in mice lacking Ron signaling.…”

Section: Functional Importance Of Ron In Murine Models Of Tumorigenesismentioning

confidence: 99%

“…In addition to Ron overexpression, two additional reports have documented the in vivo significance of Ron signaling in tumor initiation and progression by performing loss-offunction analyses [44,48]. In one model, gene targeted mice lacking functional Ron were crossed with mice that are predisposed to breast cancer and metastasis by the mammary specific overexpression of polyoma virus middle T antigen (pMT) [44].…”

Section: Functional Importance Of Ron In Murine Models Of Tumorigenesismentioning

confidence: 99%

Ron-Receptor Tyrosine Kinase In Tumorigenesis and Metastasis

2007

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SummaryThe 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 β-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 taken to successfully block Ron activity and function, and given this 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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“…The Ron oncogenic potential can be unleashed by overexpression both in vitro (11) and in vivo (18) where it induces an increase in cellular proliferation, motility, and invasion and drives tumourigenesis. Ron synergizes with other oncogenes, that is, polyoma virus middle T (19) and RAS (20), enhancing their oncogenic potential. From an opposite but complementary perspective Ron downregulation by siRNA in a panel of colon cancer cells impairs proliferation and motility and induces apoptosis (21).…”

Section: Introductionmentioning

confidence: 99%

Ron Kinase Transphosphorylation Sustains MET Oncogene Addiction

et al. 2011

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Receptors for the scatter factors HGF and MSP that are encoded by the MET and RON oncogenes are key players in invasive growth. Receptor cross-talk between Met and Ron occurs. Amplification of the MET oncogene results in kinase activation, deregulated expression of an invasive growth phenotype, and addiction to MET oncogene signaling (i.e., dependency on sustained Met signaling for survival and proliferation). Here we show that cancer cells addicted to MET also display constitutive activation of the Ron kinase. In human cancer cell lines coexpressing the 2 oncogenes, Ron is specifically transphosphorylated by activated Met. In contrast, Ron phosphorylation is not triggered in cells harboring constitutively active kinase receptors other than Met, including Egfr or Her2. Furthermore, Ron phosphorylation is suppressed by Met-specific kinase inhibitors (PHA-665752 or JNJ-38877605). Last, Ron phosphorylation is quenched by reducing cell surface expression of Met proteins by antibody-induced shedding. In MET-addicted cancer cells, short hairpin RNA-mediated silencing of RON expression resulted in decreased proliferation and clonogenic activity in vitro and tumorigenicity in vivo. Our findings establish that oncogene addiction to MET involves Ron transactivation, pointing to Ron kinase as a target for combinatorial cancer therapy. Cancer Res; 71(5); 1945-55. Ó2011 AACR.

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Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

Cited by 26 publications

References 35 publications

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

Ron-Receptor Tyrosine Kinase In Tumorigenesis and Metastasis

Ron Kinase Transphosphorylation Sustains MET Oncogene Addiction

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