TY - JOUR
T1 - CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells
AU - Zhang, Jing Min
AU - Murakumo, Yoshiki
AU - Hagiwara, Sumitaka
AU - Jiang, Ping
AU - Mii, Shinji
AU - Kalyoncu, Emir
AU - Saito, Shoji
AU - Suzuki, Chikage
AU - Sakurai, Yasutaka
AU - Numata, Yoshiko
AU - Yamamoto, Toshimichi
AU - Takahashi, Masahide
N1 - Funding Information:
We thank Mr. K. Imaizumi, Mr. K. Uchiyama, and Mrs. K. Ushida for technical assistance. This work was supported by Grants-in-Aid for Global Center of Excellence (GCOE) research commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (to MT) and for Scientific Research (C) commissioned by MEXT of Japan (21590435 to YM).
Publisher Copyright:
© 2015 The Authors . Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
PY - 2015/4/3
Y1 - 2015/4/3
N2 - CD109 is a glycosylphosphatidylinositol-anchored cell surface protein that is frequently detected in squamous cell carcinomas. CD109 is a negative regulator of TGF-β1 signaling in human keratinocytes, and the N-terminal fragment of CD109 secreted from cells after cleavage by the furin protease is important for modulating TGF-β1 signaling. Previously, we found that CD109 is expressed in human glioblastoma cells; however, the role of CD109 in glioblastoma cells is not established. Here, we describe the effects of CD109 in human glioblastoma cell lines. Three glioblastoma cell lines, SK-MG-1, U251MG and MG178, were tested and CD109 overexpression attenuated TGF-β1 signaling and enhanced EGF signaling in SK-MG-1, but not in U251MG or MG178. The N-terminal CD109 fragment in SK-MG-1 was hyperglycosylated compared with that in MG178 or U251MG. The conditioned medium of CD109-overexpressing SK-MG-1, containing the secreted N-terminal CD109, had a negative effect on TGF-β1 signaling in wild-type SK-MG-1 and MG178, whereas it did not show any effect on EGF signaling. In addition, cell surface CD109 interacts with EGF receptor in SK-MG-1 overexpressing CD109, and exhibited enhanced cell migration and invasion. These findings suggest that CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 cells and that the membrane-anchored CD109 may play major roles in the EGF signaling pathway.
AB - CD109 is a glycosylphosphatidylinositol-anchored cell surface protein that is frequently detected in squamous cell carcinomas. CD109 is a negative regulator of TGF-β1 signaling in human keratinocytes, and the N-terminal fragment of CD109 secreted from cells after cleavage by the furin protease is important for modulating TGF-β1 signaling. Previously, we found that CD109 is expressed in human glioblastoma cells; however, the role of CD109 in glioblastoma cells is not established. Here, we describe the effects of CD109 in human glioblastoma cell lines. Three glioblastoma cell lines, SK-MG-1, U251MG and MG178, were tested and CD109 overexpression attenuated TGF-β1 signaling and enhanced EGF signaling in SK-MG-1, but not in U251MG or MG178. The N-terminal CD109 fragment in SK-MG-1 was hyperglycosylated compared with that in MG178 or U251MG. The conditioned medium of CD109-overexpressing SK-MG-1, containing the secreted N-terminal CD109, had a negative effect on TGF-β1 signaling in wild-type SK-MG-1 and MG178, whereas it did not show any effect on EGF signaling. In addition, cell surface CD109 interacts with EGF receptor in SK-MG-1 overexpressing CD109, and exhibited enhanced cell migration and invasion. These findings suggest that CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 cells and that the membrane-anchored CD109 may play major roles in the EGF signaling pathway.
UR - http://www.scopus.com/inward/record.url?scp=84925515948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925515948&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2015.02.093
DO - 10.1016/j.bbrc.2015.02.093
M3 - Article
C2 - 25724945
AN - SCOPUS:84925515948
SN - 0006-291X
VL - 459
SP - 252
EP - 258
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -