ezrin在食管癌进展中的PI3K-AKT信号通路调控作用

IF 2.5 3区 生物学
Yuefeng Zhang, Qifeng Zhao, Jie Du
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引用次数: 0

摘要

背景:食管癌(EC)的进展与癌基因的异常激活和抑癌基因的抑制有关。EZR基因编码ezrin,它在癌细胞中高度激活和上调,有助于它们的侵袭潜力。本研究旨在阐明ezrin在EC进展中的作用,并特别关注PI3K-AKT信号通路。方法:在ECA109细胞中沉默EZR基因的表达,评估多种激酶磷酸化水平的变化,通过生物信息学分析确定EZR相关的信号通路。通过体外功能实验研究EZR沉默对细胞增殖、凋亡、迁移和侵袭的影响。结果:与对照细胞相比,EZR敲低的细胞显示AKT1/2/3 (S473)、EGFR (Y1086)、PLC-γ1 (Y783)、Src (Y419)、STAT5a/b (Y694/Y699)、Yes (Y426)和β-Catenin的磷酸化显著降低。这些发现表明PI3K-AKT信号通路是ezrin活性的关键下游介质。用AKT通路激活剂处理后,EZR敲低导致的AKT磷酸化抑制被逆转,证实了该信号轴的参与。功能上,EZR沉默显著降低EC细胞的增殖、迁移和侵袭,增加凋亡。在一定程度上,这些作用通过AKT通路的同时激活而减弱。综上所述,这些数据表明ezrin通过PI3K-AKT信号通路调节EC中的关键致癌过程。结论:Ezrin通过调控PI3K-AKT信号级联参与EC的进展,影响细胞增殖、凋亡、迁移和侵袭。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulatory role of ezrin in esophageal cancer progression via the PI3K-AKT signaling pathway.

Background: The progression of esophageal cancer (EC) has been associated with aberrant activation of oncogenes and suppression of tumor suppressor genes. The EZR gene encodes ezrin, which is highly activated and upregulated in cancer cells, contributing to their invasive potential. This study aimed to elucidate the role of ezrin in EC progression, with a specific focus on the PI3K-AKT signaling pathway.

Method: Expression of the EZR gene was silenced in ECA109 cells to assess changes in the phosphorylation levels of multiple kinases Bioinformatics analyses were conducted to identify ezrin-associated signaling pathways. In vitro functional assays were performed to investigate the effects of EZR silencing on cell proliferation, apoptosis, migration, and invasion.

Results: Cells with EZR knockdown demonstrated markedly decreased phosphorylation of AKT1/2/3 (S473), EGFR (Y1086), PLC-γ1 (Y783), Src (Y419), STAT5a/b (Y694/Y699), Yes (Y426), and β-Catenin, relative to control cells. These findings indicate that the PI3K-AKT signaling pathway is a critical downstream mediator of ezrin activity. The inhibition of AKT phosphorylation resulting from EZR knockdown was reversed upon treatment with an AKT pathway activator, confirming the involvement of this signaling axis. Functionally, EZR silencing significantly reduced EC cell proliferation, migration, and invasion, and increased apoptosis. These effects were attenuated, in part, by concurrent activation of the AKT pathway. Collectively, the data suggest that ezrin modulates key oncogenic processes in EC through the PI3K-AKT signaling pathway.

Conclusion: Ezrin contributes to the progression of EC through modulation of the PI3K-AKT signaling cascade, influencing cellular proliferation, apoptosis, migration, and invasion.

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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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