Regulation of transcription factor suppresses malignant properties of cancer cells with changes in glycosylation

转录因子的调节通过糖基化的变化抑制癌细胞的恶性特性

• 批准号: 23590070
• 负责人: SATO Takeshi
• 金额: $ 3.49万
• 依托单位: Nagaoka University of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590070/
• 关键词: 転写因子; がん; 悪性形質; 腫瘍形成; 細胞運動; 糖鎖; 糖タンパク質; シグナル伝達

In this grant, we established the Sp1-knockdown cells from A549 human lung carcinoma cells by RNAi technique, and examined the relationship between protein glycosylation and malignant properties. Lectin blot analysis showed that decreased galactosylation of N-glycans is observed for E-cadherin in the Sp1-knockdown cells. The gene expression level of beta-1,4-GalT I decreased significantly by knockdown of Sp1. Analysis of the promoter region of the human beta-1,4-GalT I gene revealed that the Sp1-binding site are critical for the expression of the gene. Moreover, knockdown of Sp1 resulted in suppression of the tumorigenic potential and migratory activity of A549 cells. Furthermore, the EGF receptor signaling was reduced by knockdown of Sp1. The study indicates that the malignant properties of cancer cells can be suppressed by regulating Sp1 through changes in protein glycosylation, and suggests that Sp1 may be a potential target for cancer therapy.

本课题利用RNA干扰技术从A549人肺癌细胞中建立了Sp1基因敲减细胞，并研究了蛋白质糖基化与恶性性质之间的关系。凝集素印迹分析表明，减少半乳糖基化的N-聚糖观察到E-钙粘蛋白在Sp1敲低细胞。β-1，4-GalT I的基因表达水平通过敲低Sp1而显著降低。对人β-1，4-GalT I基因启动子区的分析表明，Sp1结合位点对该基因的表达至关重要。此外，敲低Sp1导致A549细胞的致瘤潜力和迁移活性的抑制。此外，EGF受体信号转导通过敲低Sp1而减少。该研究表明，通过蛋白质糖基化的变化调节Sp1可以抑制癌细胞的恶性特性，并表明Sp1可能是癌症治疗的潜在靶点。

项目成果

ヒトβ4-ガラクトース転移酵素1遺伝子のプロモーター領域における転写因子Sp1結合部位の機能解析

人β4-半乳糖基转移酶1基因启动子区转录因子Sp1结合位点的功能分析

• 发表时间: 2013
• 作者: 丹下梨穂;古川清;佐藤武史
• 通讯作者: 佐藤武史

Glycoscience: Biology and Medicine

• DOI: 10.1007/978-4-431-54841-6
• 发表时间: 2015
• 作者: N. Taniguchi;T. Endo;G. Hart;P. Seeberger;P. Seeberger;Chi-Huey Wong;Chi‐Huey Wong

Lectins/Methods in Molecular Biology

凝集素/分子生物学方法

• 发表时间: 2014
• 作者: Sato;T.
• 通讯作者: T.

Handbook of Glycosyltransferase and Related Genes

糖基转移酶及相关基因手册

• 发表时间: 2014
• 作者: Furukawa;K.;Clausen;H.;and Sato;T.
• 通讯作者: T.

Changes in N-glycosylation and migration of A549 human lung carcinoma cells by knockdown of transcription factor Sp1

敲低转录因子Sp1导致A549人肺癌细胞N-糖基化和迁移的变化

• 发表时间: 2011
• 作者: Sato;T.;and Furukawa;K
• 通讯作者: K