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

Research output: Contribution to journalArticle

15 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 languageEnglish
Pages (from-to)161-169
Number of pages9
JournalCancer Letters
Volume315
Issue number2
DOIs
Publication statusPublished - 2012 Feb 28

Fingerprint

Squamous Cell Carcinoma
Mutation
Neoplasms
Cadherins
Endocytosis
Matrix Metalloproteinases
Cytosol
Lipids

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{847906bde0a241c59cedb7adb5526383,
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",
year = "2012",
month = "2",
day = "28",
doi = "10.1016/j.canlet.2011.09.036",
language = "English",
volume = "315",
pages = "161--169",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

A novel gain-of-function mutation of TGF-β receptor II promotes cancer progression via delayed receptor internalization in oral squamous cell carcinoma. / Park, Iha; Son, Hwa Kyung; Che, Zhong Min; Kim, Jin.

In: Cancer Letters, Vol. 315, No. 2, 28.02.2012, p. 161-169.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel gain-of-function mutation of TGF-β receptor II promotes cancer progression via delayed receptor internalization in oral squamous cell carcinoma

AU - Park, Iha

AU - Son, Hwa Kyung

AU - Che, Zhong Min

AU - Kim, Jin

PY - 2012/2/28

Y1 - 2012/2/28

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.

UR - http://www.scopus.com/inward/record.url?scp=84355162840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84355162840&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2011.09.036

DO - 10.1016/j.canlet.2011.09.036

M3 - Article

VL - 315

SP - 161

EP - 169

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -