Redzic Jasmina S, Gomez Joe D, Hellwinkel Justin E, Anchordoquy Thomas J, Graner Michael W
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
Department of Neurosurgery, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
Oncotarget. 2016 Jul 26;7(30):47831-47847. doi: 10.18632/oncotarget.10032.
Brain tumors such as high grade gliomas are among the deadliest forms of human cancers. The tumor environment is subject to a number of cellular stressors such as hypoxia and glucose deprivation. The persistence of the stressors activates the unfolded proteins response (UPR) and results in global alterations in transcriptional and translational activity of the cell. Although the UPR is known to effect tumorigenesis in some epithelial cancers, relatively little is known about the role of the UPR in brain tumors. Here, we evaluated the changes at the molecular level under homeostatic and stress conditions in two glioma cell lines of differing tumor grade. Using mass spectrometry analysis, we identified proteins unique to each condition (unstressed/stressed) and within each cell line (U87MG and UPN933). Comparing the two, we find differences between both the conditions and cell lines indicating a unique profile for each. Finally, we used our proteomic data to identify the predominant pathways within these cells under unstressed and stressed conditions. Numerous predominant pathways are the same in both cell lines, but there are differences in biological and molecular classifications of the identified proteins, including signaling mechanisms, following UPR induction; we see that relatively minimal proteomic alterations can lead to signaling changes that ultimately promote cell survival.
脑肿瘤，如高级别胶质瘤，是人类癌症中最致命的类型之一。肿瘤环境会受到多种细胞应激源的影响，如缺氧和葡萄糖剥夺。这些应激源的持续存在会激活未折叠蛋白反应（UPR），并导致细胞转录和翻译活性的整体改变。虽然已知UPR在某些上皮癌中影响肿瘤发生，但关于UPR在脑肿瘤中的作用却知之甚少。在这里，我们评估了两种不同肿瘤级别的胶质瘤细胞系在稳态和应激条件下分子水平的变化。通过质谱分析，我们鉴定了每种条件（未应激/应激）以及每个细胞系（U87MG和UPN933）中独特的蛋白质。比较两者，我们发现条件和细胞系之间都存在差异，表明每个都有独特的特征。最后，我们利用蛋白质组学数据确定了这些细胞在未应激和应激条件下的主要信号通路。两个细胞系中许多主要信号通路是相同的，但在UPR诱导后，所鉴定蛋白质的生物学和分子分类存在差异，包括信号传导机制；我们发现相对微小的蛋白质组改变可导致信号变化，最终促进细胞存活。
