RRC ID 56570
著者 Kamil M, Shinsato Y, Higa N, Hirano T, Idogawa M, Takajo T, Minami K, Shimokawa M, Yamamoto M, Kawahara K, Yonezawa H, Hirano H, Furukawa T, Yoshimoto K, Arita K.
タイトル High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme.
ジャーナル Br J Cancer
Abstract 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.
巻・号 120(8)
ページ 819-826
公開日 2019-4-1
DOI 10.1038/s41416-019-0413-x
PII 10.1038/s41416-019-0413-x
PMID 30867563
PMC PMC6474268
MeSH Actin Cytoskeleton / genetics Biomarkers, Tumor / genetics* Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Female Filamins / genetics* Gene Expression Regulation, Neoplastic / genetics Glioblastoma / epidemiology Glioblastoma / genetics* Glioblastoma / pathology Humans Kaplan-Meier Estimate Male Matrix Metalloproteinase 2 / genetics Neoplasm Invasiveness / genetics* Neoplasm Invasiveness / pathology
IF 5.416
引用数 2
リソース情報
遺伝子材料 NRCD human cDNA clone ARi57A02 (HKR182802) pENTR4-H1 (RDB04395) CS-RfA-EVBsd (RDB06090)