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

Iha Park; Hwa Kyung Son; Zhong Min Che; Jin Kim

doi:10.1016/j.canlet.2011.09.036

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

Iha Park, Hwa Kyung Son, Zhong Min Che, Jin Kim

Department of Oral Pathology

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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
Pages (from-to)	161-169
Number of pages	9
Journal	Cancer Letters
Volume	315
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2011.09.036
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

UN SDGs

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

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.",

author = "Iha Park and Son, {Hwa Kyung} and Che, {Zhong Min} and Jin Kim",

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).",

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AU - Che, Zhong Min

AU - Kim, Jin

N1 - 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).

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N2 - 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.

AB - 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.

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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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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