Article ID Journal Published Year Pages File Type
2113536 Cancer Letters 2012 9 Pages PDF
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.

► We present a novel gain-of-function mutation of TGF-β receptor II (TβRII) in human oral squamous cell carcinoma. ► This mutation of TβRII enhances TGF-β signaling. ► Mutation of TβRII induces higher migratory and invasive capabilities. ► Enhanced TGF-β signaling by this mutation is due to delayed TβRII internalization.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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