High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme
High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme
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DOI：
10.1038/s41416-019-0413-x
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发表时间：
2019-04-16
影响因子：
8.8
通讯作者：
Arita, Kazunori
中科院分区：
文献类型：
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作者：
Kamil, Muhammad;Shinsato, Yoshinari;Arita, Kazunori
背景技术背景：多形性胶质母细胞瘤（GBM）是成人中最常见的脑恶性肿瘤，通常具有侵袭性且不可治愈，即使采用多种治疗方式和药物。微丝蛋白（FLN）是一组肌动蛋白结合蛋白，调节细胞中的肌动蛋白细胞骨架。然而，FLN在恶性肿瘤中的作用，特别是在GBM中的作用尚不清楚。方法：使用鹿儿岛大学医院的GBM患者（n = 90）和来自癌症基因组图谱（TCGA）的数据（n = 153），通过Kaplan-Meier分析评价了FLN表达与GBM总生存率之间的关系。为了评估FLNC在GBM中的功能，使用过表达FLNC的U251 MG和LN 299 GBM细胞以及shRNA介导的FLNC敲低的KNS 81和U87 MG细胞，用Transwell和Matrigel侵袭测定法检查细胞迁移和侵袭。明胶酶谱法测定用于估计基质金属蛋白酶（MMP）2 activity.RESULTS：在计算机分析的GBM患者的数据从TCGA和免疫组化分析的临床GBM标本显示，FLNC表达增加与患者预后不良。FLNC在GBM细胞系中的过表达与侵袭性增强呈正相关，但与迁移性无关，并伴随MMP 2的上调。结论：FLNC是GBM进展的潜在治疗靶点和生物标志物。
BACKGROUND: Glioblastoma multiforme (GBM), the most common brain malignancy in adults, is generally aggressive and incurable, even with multiple treatment modalities and agents. Filamins (FLNs) are a group of actin-binding proteins that regulate the actin cytoskeleton in cells. However, the role of FLNs in malignancies-particularly in GBM-is unclear.METHODS: The relation between FLNC expression and overall survival in GBM was evaluated by the Kaplan-Meier analysis using GBM patients from the Kagoshima University Hospital (n = 90) and data from the Cancer Genome Atlas (TCGA) (n = 153). To assess FLNC function in GBM, cell migration and invasion were examined with Transwell and Matrigel invasion assays using FLNC-overexpressing U251MG and LN299 GBM cells, and ShRNA-mediated FLNC knocked-down KNS81 and U87MG cells. The gelatin zymography assay was used to estimate matrix metalloproteinase (MMP) 2 activity.RESULTS: In silico analysis of GBM patient data from TCGA and immunohistochemical analyses of clinical GBM specimens revealed that increased FLNC expression was associated with poor patient prognosis. FLNC overexpression in GBM cell lines was positively correlated with enhanced invasiveness, but not migration, and was accompanied by upregulation of MMP2.CONCLUSIONS: FLNC is a potential therapeutic target and biomarker for GBM progression.