New invasion and migration mechanisms associated with FMNL1 in glioblastoma

• Project/Area Number: 18K16590
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kagoshima University
• Principal Investigator: HIGA Nayuta 鹿児島大学, 鹿児島大学病院, 医員 (90792200)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 膠芽腫 / FMNL1 / 浸潤・遊走能 / invasion / migration / glioblastoma / mDia1 (DIAPH1) / GM130 (GOLGA2) / Mesenchymal subtype / mDial / GM130 / Glioblastoma / フォルミンファミリー

Outline of Final Research Achievements

This study was conducted to elucidate the FMNL1 function in the acquisition of malignant features of GBM. Our study showed FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (P < 0.001). Furthermore, 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 neural-to-mesenchymal transition. Contrarily, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fibers assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression.

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は、悪性脳腫瘍の中で最も頻度が高く、高い増殖能、遊走・浸潤能が特徴である。FMNL1は、膠芽腫が悪性性質を獲得する上で重要な役割を果たしている可能性がある分子として我々が見出したアクチン重合因子である。膠芽腫の治療において、高い浸潤・遊走能は克服しなければならない大きな問題である。本研究は、これまで明らかにされていないFMNL1を中心とした新規の浸潤・遊走機構を解明することで、膠芽腫の新たな治療標的を同定できる可能性がある。

Research Products

• [Journal Article] Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis (2019)
  • Author(s): 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
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 24 Pages: 6355-6355
  • DOI: 10.3390/ijms20246355
  • Peer Reviewed / Open Access
• [Presentation] Glioblastomaにおけるアクチン重合因子であるFormin-like 1 (FMNL1)の機能解析 (2019)
  • Author(s): 比嘉 那優大
  • Organizer: 日本分子脳神経外科学会
• [Presentation] Function of Formin-like 1 (FMNL1) in Glioblastoma Multiforme (2019)
  • Author(s): Nayuta Higa
  • Organizer: Society for neurooncology
  • Int'l Joint Research
• [Presentation] Formin-like1(FMNL1)はGlioblastomaの独立した予後不良因子であり、浸潤・遊走能を促進させる (2018)
  • Author(s): 比嘉 那優大
  • Organizer: 第77回日本脳神経外科学会総会
• [Presentation] GlioblastomaにおけるFormin-like1(FMNL1)の機能について (2018)
  • Author(s): 比嘉 那優大
  • Organizer: 第36回日本脳腫瘍学会