The regulation of glioma stem cell by the transcription factor "RBPJ" suppression in Notch signal

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: TANAKA SHINGO 金沢大学, 医学系, 助教 (40507084)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: RBPJ / Notchシグナル / グリオーマ幹細胞 / STATシグナル

Outline of Final Research Achievements

Glioblastoma is a primary malignant brain tumor and is an intractable disease with a poor prognosis. This study is a targeted therapeutic study against glioblastoma stem cells. We focused on the nuclear transcription factor RBPJ, which is an active indicator of Notch signaling. RBPJ expression was higher in glioblastoma tissue than in normal brain, and glioblastoma stem cells had higher RBPJ expression than differentiated glioblastoma cells. RBPJ inhibition of glioblastoma stem cells results in decreased cell proliferation and loss of stem cell phenotype. As a mechanism, we found that inhibition of RBPJ induced inhibition of the downstream factors interleukin 6 and STAT signal. Tumor reduction was also checked in animal studies. It suggested that inhibition of RBPJ is effective for the regulation of glioblastoma stem cells.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

Notchシグナルは様々な癌腫において幹細胞性の維持や細胞増殖などの機能を有するとされている。膠芽腫幹細胞においても同様であり、本研究ではNotchシグナルの活性に重要な核内転写因子RBPJが膠芽腫幹細胞で高発現していることを確認した。膠芽腫幹細胞のRBPJを抑制することにより腫瘍細胞の増殖遅延や幹細胞性維持機能の低下が認められた。従って、膠芽腫幹細胞制御にRBPJが重要な役割を果たしていることが示唆された。