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.
Original language | English |
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Pages (from-to) | 161-169 |
Number of pages | 9 |
Journal | Cancer Letters |
Volume | 315 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2012 Feb 28 |
Bibliographical note
Funding Information:This work was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0029702).
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research