整联蛋白αx通过PI3K / Akt信号传导介导的VEGFR2 / VEGF-A在血管内皮细胞中的过度表达刺激癌症血管生成。,Journal of Cellular Biochemistry

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整联蛋白αx通过PI3K / Akt信号传导介导的VEGFR2 / VEGF-A在血管内皮细胞中的过度表达刺激癌症血管生成。
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2018-09-14 , DOI: 10.1002/jcb.27480
Jingshu Wang _{1,

2} , Lina Yang ₂ , Fan Liang ₂ , Yaping Chen ₂ , Gong Yang _{1,

3,

4}

Affiliation

整联蛋白家族成员之一整联蛋白αx（ITGAX）通常充当细胞外基质的受体。最近，越来越多的证据表明ITGAX可能参与了树突状细胞的血管生成。本文中，我们报道了ITGAX在肿瘤发展过程中在血管生成中的直接作用。ITGAX在人脐静脉内皮细胞（HUVEC）中的过表达增强了它们的增殖，迁移和管形成，并促进了异种移植卵巢肿瘤血管生成和生长。进一步的研究表明，ITGAX的过表达激活了PI3k / Akt途径，导致c-Myc，血管内皮生长因子-A（VEGF-A）和VEGF受体2（VEGFR2）的表达增强，而细胞的治疗使用PI3K抑制剂可减少这些影响。此外，观察到c-Myc与VEGF-A启动子结合。通过共免疫沉淀（Co-IP）分析，我们证明了ITGAX与VEGFR2或磷酸化的VEGFR2之间的相互作用。人类卵巢癌标本的免疫染色表明，微血管的内皮细胞显示出VEGF-A，c-Myc，VEGFR2和PI3K信号分子的强表达。另外，在HUVEC中过表达ITGAX可能会刺激卵巢癌细胞的球状形成。我们的研究发现，ITGAX通过PI3K / Akt信号传导介导的VEGFR2 / VEGF-A过度表达来刺激癌症发展过程中的血管生成。和PI3K信号分子。另外，在HUVEC中过表达ITGAX可能会刺激卵巢癌细胞的球状形成。我们的研究发现，ITGAX通过PI3K / Akt信号传导介导的VEGFR2 / VEGF-A过度表达来刺激癌症发展过程中的血管生成。和PI3K信号分子。而且，HUVEC中ITGAX的过表达可以刺激卵巢癌细胞的球状形成。我们的研究发现，ITGAX通过PI3K / Akt信号传导介导的VEGFR2 / VEGF-A过度表达来刺激癌症发展过程中的血管生成。

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Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel endothelial cells.

Integrin alpha x (ITGAX), a member of the integrin family, usually serves as a receptor of the extracellular matrix. Recently, accumulating evidence suggests that ITGAX may be involved in angiogenesis in dendritic cells. Herein, we report a direct role of ITGAX in angiogenesis during tumor development. Overexpression of ITGAX in human umbilical vein endothelial cells (HUVECs) enhanced their proliferation, migration, and tube formation and promoted xenograft ovarian tumor angiogenesis and growth. Further study showed that overexpression of ITGAX activated the PI3k/Akt pathway, leading to the enhanced expression of c-Myc, vascular endothelial growth factor-A (VEGF-A), and VEGF receptor 2 (VEGFR2), whereas, the treatment of cells with PI3K inhibitor diminished these effects. Besides, c-Myc was observed to bind to the VEGF-A promoter. By Co-Immunoprecipitation (Co-IP) assay, we manifested the interaction between ITGAX and VEGFR2 or the phosphorylated VEGFR2. Immunostaining of human ovarian cancer specimens suggested that endothelial cells of micro-blood vessels displayed strong expression of VEGF-A, c-Myc, VEGFR2, and the PI3K signaling molecules. Also, overexpression of ITGAX in HUVECs could stimulate the spheroid formation of ovarian cancer cells. Our study uncovered that ITGAX stimulates angiogenesis through the PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression during cancer development.

更新日期：2019-11-01

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