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A novel gain-of-function mutation of TGF-β receptor II promotes cancer progression via delayed receptor internalization in oral squamous cell carcinoma.

Authors
 Iha Park  ;  Hwa-Kyung Son  ;  Zhong Min Che  ;  Jin Kim 
Citation
 CANCER LETTERS, Vol.315(2) : 161-169, 2012 
Journal Title
 CANCER LETTERS 
ISSN
 0304-3835 
Issue Date
2012
Keywords
TGF-β type II receptor ; Mutation ; Oral squamous cell carcinoma ; Migration ; Invasion
Abstract
We present a novel gain-of-function mutation of TGF-β receptor II (TβRII) found in human oral squamous cell carcinoma (OSCC). Expression of E221V/N238I mutant TβRII enhanced TGF-β signaling. Mutation of TβRII conferred cells higher migratory and invasive capabilities and MMP-2 activity. In mouse tumor model, mutant tumors exhibited poor differentiation and E-cadherin relocalization to the cytosol. Lipid-raft-dependent endocytosis of TβRII was attenuated in mutant TβRII, suggesting that enhancement of TGF-β signaling by this mutation is due to delayed TβRII internalization. Taken together, our results show a novel gain-of-function TβRII mutation, which enhances TGF-β signaling leading to more invasive phenotypic changes in human OSCC.
Full Text
http://www.sciencedirect.com/science/article/pii/S0304383511005969
DOI
10.1016/j.canlet.2011.09.036
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
Yonsei Authors
Kim, Jin(김진)
Park, Iha(박이하)
Son, Hwa Kyung(손화경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89868
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