CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.
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.
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Pharmacognosy, Jilin University School of Pharmacy, Changchun, PR China.
Jing-Min
JM
Zhang
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan. Electronic address: murakumo@med.kitasato-u.ac.jp.
Yoshiki
Y
Murakumo
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Sumitaka
S
Hagiwara
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan; The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, PR China.
Ping
P
Jiang
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shinji
S
Mii
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Emir
E
Kalyoncu
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shoji
S
Saito
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Chikage
C
Suzuki
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan.
Yasutaka
Y
Sakurai
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan.
Yoshiko
Y
Numata
Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toshimichi
T
Yamamoto
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Masahide
M
Takahashi
D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D015703:Antigens, CD; C120523:CD109 protein, human; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
CD109; EGF signaling; Glycosylation; SK-MG-1 glioblastoma cells; TGF-β1 signaling