鉴定c-Met作为γ-glutamylcyclotransferase的新目标

鉴定c-Met作为γ-glutamylcyclotransferase的新目标

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Updated: Jul 22, 2025

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

Published on: October 10, 2020

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Yumiko Saito^1,2, Keiko Taniguchi³, Hiromi Ii⁴

¹Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kawaramachi-Hirokoji Kamigyo-ku, Kyoto, 602-8566, Japan.

Scientific reports

|July 24, 2023

概括

γ-Glutamylcyclotransferase (GGCT) 倒退通过激活瘤抑制剂RB蛋白来抑制癌症生长. 这通过抑制STAT3-c-Met-MEK-ERK通路发生,这表明GGCT是潜在的癌症治疗标.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
生物化学生物化学

背景情况:

γ-Glutamylcyclotransferase (GGCT) 在各种癌症中高度表达,其抑制抑制了瘤生长.
GGCT抗瘤作用背后的精确分子机制尚未完全理解.
GGCT是癌症治疗的潜在治疗标.

研究的目的:

阐明GGCT抗瘤作用的潜在分子机制.
研究GGCT在调节参与癌症进展的关键信号通路中的作用.
确定针对GGCT的潜在治疗策略.

主要方法:

在癌细胞系 (A549,PC3) 和老鼠异种移植模型中GGCT的敲除.
对信号通路组件的分析,包括MEK-ERK,视网膜母细胞瘤基因 (RB),STAT3,c-Met和AMPK.
评估蛋白质含量,酸化状态和核表达.

主要成果:

GGCT的倒置抑制了MEK-ERK通路,并激活了RB蛋白.
GGCT的耗尽导致c-Met和STAT3酸化/核表达的减少.
同时制AMPK和GGCT调节了这些通路,表明AMPK参与其中.
在老鼠异种移植模型中,GGCT抑制降低了c-Met表达.

结论:

通过GGCT敲击,激活了瘤抑制剂RB蛋白.
这种激活是通过抑制STAT3-c-Met-MEK-ERK信号级联来调节的.
AMP激活蛋白激酶 (AMPK) 激活在观察到的效果中起作用.
向GGCT可能是癌症治疗的可行策略.

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