Document Detail


Human RON receptor tyrosine kinase induces complete epithelial-to-mesenchymal transition but causes cellular senescence.
MedLine Citation:
PMID:  17588532     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The RON receptor tyrosine kinase is a member of the MET proto-oncogene family and is important for cell proliferation, differentiation, and cancer development. Here, we created a series of Madin-Darby canine kidney (MDCK) epithelial cell clones that express different levels of RON, and have investigated their biological properties. While low levels of RON correlated with little morphological change in MDCK cells, high levels of RON expression constitutively led to morphological scattering or complete and stabilized epithelial-to-mesenchymal transition (EMT). Unexpectedly, MDCK clones expressing higher levels of RON exhibited retarded proliferation and senescence, despite increased motility and invasiveness. RON was constitutively tyrosine-phosphorylated in MDCK cells expressing high levels of RON and undergoing EMT, and the MAPK signaling pathway was activated. This study reveals for the first time that RON alone is sufficient to induce complete and stabilized EMT in MDCK cells, and overexpression of RON does not cause cell transformation but rather induces cell cycle arrest and senescence, leading to impaired cell proliferation.
Authors:
Marceline Côté; A Dusty Miller; Shan-Lu Liu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-18
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  360     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-03     Completed Date:  2007-09-05     Revised Date:  2010-12-03    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  219-25     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, McGill University, Montreal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Aging / physiology*
Cell Differentiation
Cell Line
Cell Movement
Cell Proliferation
Dogs
Epithelial Cells / cytology*,  enzymology*
Humans
Kidney / cytology,  enzymology
Mesoderm / cytology*,  enzymology*
Receptor Protein-Tyrosine Kinases / metabolism*
Grant Support
ID/Acronym/Agency:
P30 DK047754-14/DK/NIDDK NIH HHS; P30 DK047754-149001/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.1.-/RON protein; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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