Journal Article

Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase

Ming-Hai Wang, Da Wang and Yi-Qing Chen

in Carcinogenesis

Volume 24, issue 8, pages 1291-1300
Published in print August 2003 | ISSN: 0143-3334
Published online August 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg089
Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase

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The product of the RON (recepteur d'origine nantais) gene belongs to the MET proto-oncogene family, a distinct subfamily of receptor tyrosine kinases. The ligand of RON was identified as macrophage-stimulating protein (MSP), a member of the plasminogen-related growth factor family. RON is mainly expressed in cells of epithelial origin and is required for embryonic development. In vitro RON activation results in epithelial cell dissociation, migration and matrix invasion, suggesting that RON might be involved in the pathogenesis of certain epithelial cancers in vivo. Indeed, recent studies have shown that RON expression is significantly altered in several primary human cancers, including those of the breast and colon. Truncation of the RON protein has also been found in primary tumors from the gastrointestinal tract. These alterations lead to constitutive activation of RON that causes cell transformation in vitro, induces neoplasm formation in athymic nude mice, and promotes tumor metastasis into the lung. Studies employing transgenic models further demonstrated that over-expression of RON in lung epithelial cells results in multiple tumor formation with features of large cell undifferentiated carcinoma. The oncogenic activities of RON are mediated by RON-transduced signals that promote unbalanced cell growth and transformation leading to tumor development. Thus, abnormal accumulation and activation of RON could play a critical role in vivo in the progression of certain malignant human epithelial cancers.

Keywords: BAC, bronchioloalveolar carcinoma; ECM, extracellular matrix; EMT, epithelial-mesenchymal transition; Grb-2, growth factor receptor bound protein 2; HGF, hepatocyte growth factor; HGFL, hepatocyte growth factor-like; JNK; jun N-terminal kinase; JSRV, jaagsiekte sheep retrovirus; MAPK, mitogen activated protein kinase; MDCK, Madin–Darby canine kidney; MSP, macrophage-stimulating protein; NF-κB, nuclear factor-κB; PI-3K, phosphotidylinositol-3 kinase; RON, recepteur d'origine nantais; Sea, sarcoma, erythroblastosis, and anemia; SF, scatter factor; Smad, Sma and mothers against decapentaplegic homolog; TGF, transforming growth factor; Tpr, translocated promoter region

Journal Article.  8718 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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