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

Muhammad Kamil, Yoshinari Shinsato, Nayuta Higa, Takuro Hirano, Masashi Idogawa, Tomoko Takajo, Kentaro Minami, Michiko Shimokawa, Masatatsu Yamamoto, Kohichi Kawahara, Hajime Yonezawa, Hirofumi Hirano, Tatsuhiko Furukawa, Koji Yoshimoto, Kazunori Arita

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)819-826
Number of pages8
JournalBritish journal of cancer
Volume120
Issue number8
DOIs
Publication statusPublished - Apr 16 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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