Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Int J Mol Sci. 2019 Dec 17;20(24):6355. doi: 10.3390/ijms20246355.
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 ( < 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.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性恶性脑肿瘤，其特征为快速增殖、侵袭性迁移以及向正常脑组织浸润。formin 蛋白参与了这些过程。然而，formin 样蛋白 1（FMNL1）在癌症中的作用仍不清楚。我们使用免疫组织化学研究了胶质母细胞瘤样本中的 FMNL1 表达。我们试图分析 FMNL1 表达与临床病理变量和患者生存之间的相关性。我们使用迁移和侵袭实验来验证 FMNL1 对胶质母细胞瘤细胞系的影响。从癌症基因组图谱下载微阵列数据，并使用基因集富集分析（GSEA）进行分析。FMNL1 是 217 例胶质母细胞瘤病例队列中不良预后的独立预测因子（<0.001）。在间充质亚型中，FMNL1 的表达明显更高。FMNL1 的上调和下调与 GSEA 中的间充质和原神经标志物相关。这些数据突出了 FMNL1 在神经到间充质转化中的重要作用。相反，FMNL1 的下调通过 DIAPH1 和 GOLGA2 分别抑制了胶质母细胞瘤的迁移和侵袭。FMNL1 的下调还抑制了肌动蛋白纤维的组装，诱导形态变化并减少丝状肌动蛋白。FMNL1 是一种有前途的治疗靶点，也是 GBM 进展的有用生物标志物。
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