Verano-Braga Thiago, Gorshkov Vladimir, Munthe Sune, Sørensen Mia D, Kristensen Bjarne W, Kjeldsen Frank
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Oncotarget. 2018 Jan 25;9(10):9400-9414. doi: 10.18632/oncotarget.24321. eCollection 2018 Feb 6.
Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells. We used Ingenuity Pathway Analysis (IPA) to predict upstream regulators, downstream effects and canonical pathways associated with regulated proteins. IPA analysis predicted activation of integrin-linked kinase (ILK) signaling, actin cytoskeleton signaling, and lysine demethylase 5B (KDM5B) in CSC migration. Moreover, our data suggested that microRNA-122 (miR-122) is a potential upstream regulator of GBM phenotypes as miR-122 activation was predicted for differentiated cells while its inhibition was predicted for migrating CSCs. Finally, we validated transferrin (TF) and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) as potential markers for migrating cells.
胶质母细胞瘤（GBM）是一种侵袭性很强的脑癌，预后较差，生存率低。侵袭性癌干细胞样细胞（CSCs）会导致肿瘤复发，因为它们能逃避目前的治疗方法。我们的主要目标是研究三种GBM亚群的蛋白质组，以确定GBM细胞表型背后的关键分子以及迁移细胞的潜在细胞标志物。我们使用了SuperQuant——一种增强的定量蛋白质组方法——来增加蛋白质组覆盖范围。我们发现148种蛋白质在迁移的CSCs中差异表达，199种蛋白质在分化细胞中差异表达。我们使用 Ingenuity 通路分析（IPA）来预测与调控蛋白相关的上游调节因子、下游效应和经典通路。IPA分析预测整合素连接激酶（ILK）信号、肌动蛋白细胞骨架信号和赖氨酸去甲基化酶5B（KDM5B）在CSC迁移中被激活。此外，我们的数据表明，微小RNA-122（miR-122）是GBM表型的潜在上游调节因子，因为预测分化细胞中miR-122被激活，而迁移的CSCs中miR-122被抑制。最后，我们验证了转铁蛋白（TF）和原胶原赖氨酸2-氧代戊二酸5-双加氧酶2（PLOD2）作为迁移细胞的潜在标志物。
