期刊
CANCER LETTERS
卷 315, 期 2, 页码 161-169出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.09.036
关键词
TGF-beta type II receptor; Mutation; Oral squamous cell carcinoma; Migration; Invasion
类别
资金
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0029702]
- National Research Foundation of Korea [2009-0094027] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
We present a novel gain-of-function mutation of TGF-beta receptor II (T beta RII) found in human oral squamous cell carcinoma (OSCC). Expression of E221V/N238I mutant T beta RII enhanced TGF-beta signaling. Mutation of T beta RII 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 T beta RII was attenuated in mutant T beta RII, suggesting that enhancement of TGF-beta signaling by this mutation is due to delayed T beta RII internalization. Taken together, our results show a novel gain-of-function T beta RII mutation, which enhances TGF-beta signaling leading to more invasive phenotypic changes in human OSCC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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