Next Article in Journal
Bioactive Polyphenols Modulate Enzymes Involved in Grapevine Pathogenesis and Chitinase Activity at Increasing Complexity Levels
Previous Article in Journal
The Monetite Structure Probed by Advanced Solid-State NMR Experimentation at Fast Magic-Angle Spinning
Open AccessArticle

Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis

1
Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
2
Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
3
Department of Neurosurgery, Faculty of Medicine, Airlangga University, Surabaya 60132, Indonesia
4
Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
5
Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(24), 6355; https://doi.org/10.3390/ijms20246355
Received: 12 November 2019 / Revised: 11 December 2019 / Accepted: 14 December 2019 / Published: 17 December 2019
(This article belongs to the Section Molecular Biology)
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. View Full-Text
Keywords: formin-like 1 (FMNL1); DIAPH1; GOLGA2; invasion; migration; mesenchymal subtype formin-like 1 (FMNL1); DIAPH1; GOLGA2; invasion; migration; mesenchymal subtype
Show Figures

Graphical abstract

MDPI and ACS Style

Higa, N.; Shinsato, Y.; Kamil, M.; Hirano, T.; Takajo, T.; Shimokawa, M.; Minami, K.; Yamamoto, M.; Kawahara, K.; Yonezawa, H.; Hirano, H.; Furukawa, T.; Yoshimoto, K.; Arita, K. Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis. Int. J. Mol. Sci. 2019, 20, 6355.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop