High filamin-C expression predicts enhanced invasiveness and poor outcome in glioblastoma multiforme.

Authors:
Muhammad Kamil
Muhammad Kamil
Advanced Medical and Dental Institute
Yoshinari Shinsato
Yoshinari Shinsato
Kagoshima University
Takuro Hirano
Takuro Hirano
Kyushu University
Japan
Masashi Idogawa
Masashi Idogawa
Sapporo Medical University
Japan
Kentaro Minami
Kentaro Minami
Kagoshima University
Japan
Michiko Shimokawa
Michiko Shimokawa
Kagoshima University
Japan

Br J Cancer 2019 Apr 14;120(8):819-826. Epub 2019 Mar 14.

Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

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.

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http://dx.doi.org/10.1038/s41416-019-0413-xDOI Listing
April 2019

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