CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.
CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.
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CD109 减弱 SK-MG-1 人胶质母细胞瘤细胞中的 TGF-β1 信号传导并增强 EGF 信号传导。
DOI：
10.1016/j.bbrc.2015.02.093
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发表时间：
2015
影响因子：
3.1
通讯作者：
Masahide Takahashi
中科院分区：
文献类型：
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作者：
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
CD 109是一种糖基磷脂酰肌醇锚定的细胞表面蛋白，经常在鳞状细胞癌中检测到。CD 109是人角质形成细胞中TGF-β1信号传导的负调节因子，并且在弗林蛋白酶切割后从细胞分泌的CD 109的N-末端片段对于调节TGF-β1信号传导是重要的。以前，我们发现CD 109在人胶质母细胞瘤细胞中表达;然而，CD 109在胶质母细胞瘤细胞中的作用尚未确定。在这里，我们描述了CD 109在人胶质母细胞瘤细胞系中的作用。检测了三种胶质母细胞瘤细胞系SK-MG-1、U251 MG和MG 178，并且CD 109过表达减弱了SK-MG-1中的TGF-β1信号传导并增强了EGF信号传导，但在U251 MG或MG 178中没有。与MG 178和U251 MG相比，SK-MG-1的N端CD 109片段发生了高糖基化。在野生型SK-MG-1和MG 178中，过表达CD 109的SK-MG-1的条件培养基（含有分泌的N-末端CD 109）对TGF-β1信号传导具有负面影响，而其对EGF信号传导没有任何影响。此外，细胞表面CD 109与EGF受体在SK-MG-1过表达CD 109中相互作用，并表现出增强的细胞迁移和侵袭。这些结果表明，在SK-MG-1细胞中，CD 109减弱TGF-β1信号传导并增强EGF信号传导，并且膜锚定的CD 109可能在EGF信号传导途径中起主要作用。
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.