STRIP2 受转录因子 Sp1 的调控，通过激活 PI3K/AKT/mTOR/MYC 信号通路促进肺腺癌的进展。

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Genomics Pub Date : 2024-09-01 DOI:10.1016/j.ygeno.2024.110923

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引用次数: 0

摘要

背景：肺腺癌（LUAD）患者一般预后较差。纹蛋白相互作用蛋白 2（STRIP2）在 LUAD 中的作用仍不清楚：方法：利用液相色谱-质谱分析筛选 STRIP2 结合蛋白，并通过共沉淀验证这些相互作用。双荧光素酶报告实验探索了激活STRIP2转录的转录因子。异种移植和肺转移模型评估了STRIP2在体内肿瘤生长和转移中的作用：结果：STRIP2在LUAD组织中高表达，并与预后不良有关。STRIP2在LUAD细胞中的表达能显著促进细胞在体外和体内的增殖、侵袭和迁移。从机制上讲，STRIP2通过结合AKT促进了PI3K/AKT/mTOR/MYC级联反应。此外，特异性蛋白 1 通过与 STRIP2 启动子结合，有效激活了 STRIP2 的转录。在异种移植模型中，阻断STRIP2可减少肿瘤生长和肺转移：我们的研究发现 STRIP2 是 LUAD 进展的关键驱动因素和潜在治疗靶点。

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STRIP2 is regulated by the transcription factor Sp1 and promotes lung adenocarcinoma progression via activating the PI3K/AKT/mTOR/MYC signaling pathway

Background

Patients with lung adenocarcinoma (LUAD) generally have poor prognosis. The role of striatin-interacting protein 2 (STRIP2) in LUAD remain unclear.

Methods

Liquid chromatography-mass spectrometry analyses were used to screen the STRIP2-binding proteins and co-immunoprecipitation verified these interactions. A dual luciferase reporter assay explored the transcription factor activating STRIP2 transcription. Xenograft and lung metastasis models assessed STRIP2's role in tumor growth and metastasis in vivo.

Results

STRIP2 is highly expressed in LUAD tissues and is linked to poor prognosis. STRIP2 expression in LUAD cells significantly promoted cell proliferation, invasion, and migration in vitro and in vivo. Mechanistically, STRIP2 boosted the PI3K/AKT/mTOR/MYC cascades by binding AKT. In addition, specificity protein 1, potently activated STRIP2 transcription by binding to the STRIP2 promoter. Blocking STRIP2 reduces tumor growth and lung metastasis in xenograft models.

Conclusions

Our study identifies STRIP2 is a key driver of LUAD progression and a potential therapeutic target.

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.