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High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme
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High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme
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Journal Article
High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Actin
/ Actin Cytoskeleton - genetics
/ Biomarkers, Tumor - genetics
/ Biomedical and Life Sciences
/ Cancer
/ Cell Proliferation - genetics
/ Female
/ Gelatin
/ Gene Expression Regulation, Neoplastic - genetics
/ Genomes
/ Humans
/ Male
/ Matrix Metalloproteinase 2 - genetics
/ Neoplasm Invasiveness - genetics
/ Neoplasm Invasiveness - pathology
/ Oncology
/ Patients
