Gopal Shashi K, Greening David W, Mathias Rommel A, Ji Hong, Rai Alin, Chen Maoshan, Zhu Hong-Jian, Simpson Richard J
Department of Molecular Science, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia.
Oncotarget. 2015 May 30;6(15):13718-30. doi: 10.18632/oncotarget.3764.
Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in increasing the oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells expressing YBX1 (MDCKYBX1 cells) revealed a partial EMT phenotype, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth. Subcutaneous injection of parental MDCK cells into NOD/SCID mice did not form tumours. Critically, MDCKYBX1 cells established viable tumour xenografts, and immuno-histochemical staining indicated murine vascularization by CD31+ endothelial cells. We analysed the total secretome (containing soluble and extracellular vesicles) of MDCKYBX1 cells to investigate regulation of the tumour microenvironment. YBX1 expression elevated release of secreted factors known to enhance angiogenesis (TGF-β, CSF-1, NGF, VGF, ADAM9 and ADAM17), compared to MDCK cells. Importantly, treatment with MDCKYBX1 cell-derived secretome increased recipient 2F-2B endothelial cell motility. This defines YBX1 as an oncogenic enhancer that can regulate tumour angiogenesis via release of secreted modulators into the extracellular microenvironment.
上皮-间质转化（EMT）描述了一种形态发生程序，该程序赋予上皮细胞间质细胞特性，如细胞间接触减少、细胞迁移和侵袭增加。在这里，我们研究了多效转录/剪接因子和RNA结合蛋白核酸酶敏感元件结合蛋白1（YBX1/YB-1）在增加上皮性MDCK细胞致癌潜力中的作用。对表达YBX1的MDCK细胞（MDCKYBX1细胞）的特性分析揭示了部分EMT表型，包括E-钙黏蛋白的胞质重新定位、细胞散射增加和不依赖贴壁生长。将亲代MDCK细胞皮下注射到NOD/SCID小鼠体内未形成肿瘤。至关重要的是，MDCKYBX1细胞形成了可存活的肿瘤异种移植，免疫组织化学染色显示由CD31+内皮细胞形成的小鼠血管化。我们分析了MDCKYBX1细胞的总分泌组（包含可溶性和细胞外囊泡）以研究肿瘤微环境的调节。与MDCK细胞相比，YBX1表达提高了已知可增强血管生成的分泌因子（TGF-β、CSF-1、NGF、VGF、ADAM9和ADAM17）的释放。重要的是，用MDCKYBX1细胞来源的分泌组处理可增加受体2F-2B内皮细胞的运动性。这将YBX1定义为一种致癌增强因子，它可以通过向细胞外微环境中释放分泌调节剂来调节肿瘤血管生成。
