Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis
Year: 2019
Type: article
Study design: Observational Study
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.
DOI: 10.3390/ijms20246355
Authors: 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
Institutions: Kagoshima University, Universitas Airlangga
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,824
Awards: Construction of tumor-development mice model using Abcb10 knock out mice exhibiting PPIX accumulation, gene amplification, A new mitotic surveillance mechanism in nucleolus and its application to cancer therapy, Elucidation of the role of Wnt in tumor immunity of malignant glioma and its application to therapy, Evaluation of moleclar bases for suppression of gene amplification, New invasion and migration mechanisms associated with FMNL1 in glioblastoma, glioblastomaの浸潤機構におけるFLNCを中心とした分子機構の解明, Analysis of cooperative functions of transporters andvesicle transport system in efflux of anticancer agents, Approach to regulatory mechanism of copy number variation the gene amplified., Functional significance of HDAC7 expression in glioblastoma, Investigation of pathogenic mechanisms for central post-stroke pain and its accompanying emotional disorder - evaluation of microglial activation hypothesis, Advanced Animal Model Support
OpenAlex ID: W2996534273