Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
PLoS One. 2013;8(1):e54060. doi: 10.1371/journal.pone.0054060. Epub 2013 Jan 15.
OASIS is a transcription factor similar to ATF6 that is activated by endoplasmic reticulum stress. In this study we investigated the expression of OASIS in human glioma cell lines and the effect of OASIS knock-down on the ER stress response and cell migration. OASIS mRNA was detected in three distinct glioma cell lines (U373, A172 and U87) and expression levels were increased upon treatment with ER stress-inducing compounds in the U373 and U87 lines. OASIS protein, which is glycosylated on Asn-513, was detected in the U373 and U87 glioma lines at low levels in control cells and protein expression was induced by ER stress. Knock-down of OASIS in human glioma cell lines resulted in an attenuated unfolded protein response to ER stress (reduced GRP78/BiP and GRP94 induction) and decreased expression of chondroitin sulfate proteoglycan extracellular matrix proteins, but induction of the collagen gene Col1a1 was unaffected. Cells in which OASIS was knocked-down exhibited altered cell morphology and reduced cell migration. These results suggest that OASIS is important for the ER stress response and maintenance of some extracellular matrix proteins in human glioma cells.
OASIS 是一种与 ATF6 相似的转录因子,可被内质网应激激活。本研究探讨了 OASIS 在人胶质瘤细胞系中的表达,以及 OASIS 敲低对 ER 应激反应和细胞迁移的影响。在三种不同的胶质瘤细胞系(U373、A172 和 U87)中检测到 OASIS mRNA,在 U373 和 U87 细胞系中用诱导内质网应激的化合物处理后表达水平增加。在 U373 和 U87 神经胶质瘤系中,检测到糖基化在 Asn-513 上的 OASIS 蛋白,在对照细胞中低水平表达,内质网应激诱导蛋白表达。在人神经胶质瘤细胞系中敲低 OASIS 导致 ER 应激的未折叠蛋白反应减弱(GRP78/BiP 和 GRP94 诱导减少),软骨素硫酸蛋白多糖细胞外基质蛋白表达降低,但胶原基因 Col1a1 的诱导不受影响。敲低 OASIS 的细胞表现出改变的细胞形态和减少的细胞迁移。这些结果表明,OASIS 对于人神经胶质瘤细胞中的 ER 应激反应和某些细胞外基质蛋白的维持很重要。