SOX5 induces lung adenocarcinoma angiogenesis by inducing the expression of VEGF through STAT3 signaling.
SOX5 induces lung adenocarcinoma angiogenesis by inducing the expression of VEGF through STAT3 signaling.
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SOX5通过STAT3信号传导诱导VEGF表达，从而诱导肺腺癌血管生成
DOI：
10.2147/ott.s176533
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发表时间：
2018
影响因子：
4
通讯作者：
Fu Y
中科院分区：
文献类型：
--
作者：
Chen X;Zheng Q;Li W;Lu Y;Ni Y;Ma L;Fu Y
背景与目的血管生成是肺腺癌（LAC）预后不良的主要原因。本研究旨在探讨性别决定区Y-box蛋白5 （SOX5）表达对LAC血管生成的影响，并探讨其可能的机制。患者和方法采用人脐静脉内皮细胞与A549细胞共培养成管实验考察其对血管生成的影响。利用SOX5慢病毒shRNA和SOX5过表达系统慢病毒建立不同水平表达SOX5的LAC细胞系。采用real-time qPCR和Western blot分析SOX5下游信号靶点。我们收集了90例LAC，用免疫组化方法检测了组织中SOX5和血管内皮生长因子（VEGF）的含量。结果在A549细胞中过表达SOX5可显著促进共培养人脐静脉内皮细胞成管能力。SOX5增加VEGF表达和转录信号转导激活因子3磷酸化；而SOX5对细胞外信号调节激酶和蛋白激酶B通路无影响。此外，组织芯片数据显示，SOX5与VEGF表达呈显著正相关（r=0.399， P=0.001）。结论SOX5通过激活转录3/VEGF信号转导激活因子诱导血管生成，可能成为LAC的潜在治疗靶点。
Background and objectives Angiogenesis is the main cause of lung adenocarcinoma (LAC) poor prognosis. This study aimed to investigate the effect of sex-determining region Y-box protein 5 (SOX5) expression on angiogenesis of LAC and explore its possible mechanism. Patients and methods The effect on angiogenesis was tested by tube formation assays using human umbilical vein endothelial cells cocultured with A549 cells. Lentivirus shRNA of SOX5 and lentivirus of SOX5 overexpression system were used to establish LAC cell lines, which expressed SOX5 of different levels. SOX5 downstream signaling targets were analyzed by real-time qPCR and Western blot. We collected 90 LAC cases and the tissues were examined by immunohistochemistry for SOX5 and vascular endothelial growth factor (VEGF). Results We found that SOX5 overexpression in A549 cells significantly promoted tube formation capacity of the cocultured human umbilical vein endothelial cells. SOX5 increased VEGF expression and signal transducer activator of transcription 3 phosphorylation; however, SOX5 had no effect on extracellular signal-regulated kinase and protein kinase B pathway. Furthermore, the expression of SOX5 and VEGF had a significantly positive correlation (r=0.399, P=0.001) according to the tissue microarray data. Conclusion These findings suggest that SOX5 induces angiogenesis by activating signal transducer activator of transcription 3/VEGF signaling and confer its candidacy as a potential therapeutic target in LAC.