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 | |
| Publication status | Published - 2012 Feb 28 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
}
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 journal › Article
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
C2 - 22093616
AN - SCOPUS:84355162840
VL - 315
SP - 161
EP - 169
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -