Identification of a novel cancer therapy target molecule by elucidating the physiological function of the orphan transporter

通过阐明孤儿转运蛋白的生理功能鉴定新型癌症治疗靶分子

• 批准号: 24890170
• 负责人: ITO Shingo
• 金额: $ 1.91万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-08-31 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24890170/
• 关键词: オーファントランスポーター; タンパク質翻訳後修飾; がん治療標的分子; 腫瘍形成; 細胞内代謝調節; O-GlcNAc化修飾; 定量的標的プロテオミクス; がん治療

We detected the expression of SLC22A18, an orphan transporter and tumor suppressor gene, in organelle membranes, but not within the plasma membrane. We showed that the level of UDP-GlcNAc, an O-GlcNAc modification substrate, is higher in cells stably expressing SLC22A18 than in mock cells. In addition, the levels of O-GlcNAc-modified proteins detected using western blot analysis are increased in cells stably expressing SLC22A18. We found that SLC22A18 knockdown in some tumor cell types increased cell proliferation rates, suggesting that a relationship exists between low SLC22A18 levels and acceleration of tumorigenesis.

我们在细胞器膜中检测到孤儿转运蛋白和肿瘤抑制基因 SLC22A18 的表达，但在质膜内未检测到。我们发现，稳定表达 SLC22A18 的细胞中 UDP-GlcNAc（一种 O-GlcNAc 修饰底物）的水平高于模拟细胞。此外，使用蛋白质印迹分析检测到的 O-GlcNAc 修饰蛋白的水平在稳定表达 SLC22A18 的细胞中有所增加。我们发现某些肿瘤细胞类型中 SLC22A18 敲低会增加细胞增殖率，这表明低 SLC22A18 水平与肿瘤发生加速之间存在关系。