Human RON receptor tyrosine kinase induces complete epithelial-to-mesenchymal transition but causes cellular senescence
- Department of Microbiology and Immunology, McGill University, Montreal (Canada)
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109 (United States)
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.
- OSTI ID:
- 20991498
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 360, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.06.033; PII: S0006-291X(07)01273-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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