Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Genomics. 2024 Sep;116(5):110923. doi: 10.1016/j.ygeno.2024.110923. Epub 2024 Aug 25.
Patients with lung adenocarcinoma (LUAD) generally have poor prognosis. The role of striatin-interacting protein 2 (STRIP2) in LUAD remain unclear.
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.
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.
Our study identifies STRIP2 is a key driver of LUAD progression and a potential therapeutic target.
肺腺癌（LUAD）患者的预后通常较差。STRIP2 在 LUAD 中的作用尚不清楚。
采用液相色谱-质谱分析筛选 STRIP2 结合蛋白，并用免疫共沉淀验证这些相互作用。双荧光素酶报告基因分析探讨了激活 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。
STRIP2 在 LUAD 组织中高表达，与不良预后相关。LUAD 细胞中的 STRIP2 表达显著促进了体外和体内的细胞增殖、侵袭和迁移。机制上，STRIP2 通过与 AKT 结合来增强 PI3K/AKT/mTOR/MYC 级联反应。此外，特异性蛋白 1 通过结合 STRIP2 启动子，强力激活 STRIP2 转录。阻断 STRIP2 可减少异种移植模型中的肿瘤生长和肺转移。
本研究确定 STRIP2 是 LUAD 进展的关键驱动因素，也是潜在的治疗靶点。
