CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells

• DOI: 10.1016/j.bbrc.2015.02.093
• Publication Date: 2015-02-25T04:28:09Z
• Authors: Jing-Min Zhang; Yoshiki Murakumo; Sumitaka Hagiwara; Ping Jiang; Shinji Mii; Emir Kalyoncu; Shoji Saito; Chikage Suzuki; Yasutaka Sakurai; Yoshiko Numata; Toshimichi Yamamoto; Masahide Takahashi
• Keywords: Keratinocytes; 0301 basic medicine; Glycosylation; Biophysics; GPI-Linked Proteins; Biochemistry; Transforming Growth Factor beta1; EGF signaling; 03 medical and health sciences; Antigens, CD; Cell Movement; Cell Line, Tumor; SK-MG-1 glioblastoma cells; Humans; Neoplasm Invasiveness; Molecular Biology; TGF-β1 signaling; Epidermal Growth Factor; Cell Biology; CD109; Peptide Fragments; Recombinant Proteins; Neoplasm Proteins; ErbB Receptors; Glioblastoma; Signal Transduction

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.