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.
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Project, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Iha
authors.initials: I
authors.lastname: Park
authors.forename: Hwa-Kyung
authors.initials: HK
authors.lastname: Son
authors.forename: Zhong Min
authors.initials: ZM
authors.lastname: Che
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000503:physiopathology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation; D016133:Polymerase Chain Reaction; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018125:Receptors, Transforming Growth Factor beta