ANGPTL3 inhibits renal cell carcinoma metastasis by inhibiting VASP phosphorylation
ANGPTL3 inhibits renal cell carcinoma metastasis by inhibiting VASP phosphorylation
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ANGPTL3通过抑制VASP磷酸化抑制肾细胞癌转移
DOI：
10.1016/j.bbrc.2019.06.120
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发表时间：
2019-08-27
影响因子：
3.1
通讯作者：
Wang, Linhui
中科院分区：
文献类型：
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作者：
Zhao, Tangliang;Liang, Xiaolong;Wang, Linhui
血管生成素样蛋白（ANGPTL）包括一组结构上类似于血管生成素的蛋白质。在我们以前的研究中，我们发现ANGPTL 3可以抑制肾细胞癌（RCC）中索拉非尼耐药。根据基于癌症基因组图谱（TCGA）数据的生物信息学分析，我们发现ANGPTL 3在RCC组织中的表达显著低于邻近组织，并且ANGPTL 3水平较低的患者的无病生存期和总生存期显著短于ANGPTL 3水平较高的患者。与这些结果一致，我们证明RCC组织表现出比配对的相邻组织更低的ANGPTL 3 mRNA和蛋白表达水平。此外，我们发现ANGPTL 3上调与RCC患者更好的临床结局相关。ANGPTL 3过表达抑制肾癌细胞的转移能力。在机制上，ANGPTL 3与血管舒张剂刺激的磷蛋白（VASP）结合，并抑制其在RCC细胞中氨基酸157处的磷酸化。ANGPTL 3表达和VASP-157磷酸化可联合预测RCC患者的预后。总之，我们的研究结果描述了ANGPTL 3在抑制RCC转移中的作用，从而为RCC治疗和预后提供了新的分子标志物。(C)2019爱思唯尔公司All rights reserved.
Angiopoietin-like proteins (ANGPTLs) comprise a group of proteins that are structurally similar to angiopoietins. In our previous studies, we found that ANGPTL3 can inhibit sorafenib resistance in renal cell carcinoma (RCC). According to bioinformatics analysis based on data in the Cancer Genome Atlas (TCGA), we found that expression of ANGPTL3 was significantly lower in RCC tissues than in adjacent tissues and that disease-free survival and overall survival were significantly shorter in patients with lower ANGPTL3 levels than in those with higher ANGPTL3 levels. Consistent with these results, we demonstrated that RCC tissues exhibited lower ANGPTL3 mRNA and protein expression levels than paired adjacent tissues. Moreover, we found that ANGPTL3 upregulation was associated with better clinical outcomes in RCC patients. ANGPTL3 overexpression inhibited the metastatic ability in RCC cells. Mechanistically, ANGPTL3 binds to vasodilator-stimulated phosphoprotein (VASP) and inhibits its phosphorylation at amino acid 157 in RCC cells. Finally, ANGPTL3 expression and VASP-157 phosphorylation may be combined to predict the prognosis of RCC patients. Overall, our findings describe the role of ANGPTL3 in inhibiting RCC metastasis and thus provide new molecular markers for RCC treatment and prognosis. (C) 2019 Elsevier Inc. All rights reserved.