Formin-like 1 (FMNL1) is associated with glioblastoma multiforme mesenchymal subtype and independently predicts poor prognosis

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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is characterized by rapid proliferation, aggressive migration, and invasion into normal brain tissue. Formin proteins have been implicated in these processes. However, the role of formin-like 1 (FMNL1) in cancer remains unclear. We studied FMNL1 expression in glioblastoma samples using immunohistochemistry. We sought to analyze the correlation between FMNL1 expression, clinicopathologic variables, and patient survival. Migration and invasion assays were used to verify the effect of FMNL1 on glioblastoma cell lines. Microarray data were downloaded from The Cancer Genome Atlas and analyzed using gene set enrichment analysis (GSEA). FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (p < 0.001). FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in the neural-to-mesenchymal transition. Conversely, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fiber assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.

Original languageEnglish
Article number6355
JournalInternational journal of molecular sciences
Volume20
Issue number24
DOIs
Publication statusPublished - Dec 2 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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