Elucidation of glioma malignant transformation mechanism of integrin activation by Talin-1

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07624
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kansai Medical University
• Principal Investigator: IKEDA Yoshiki 関西医科大学, 医学部, 助教 (10633026)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: インテグリン / 神経膠芽腫 / 阻害薬

Outline of Final Research Achievements

The purpose of this research project is to clarify the mechanism of proliferation by integrin signaling in glioblastoma (GBM). To achieve this goal, we have developed drugs that suppress integrin. We found that this drug possessed a GBM cell-specific growth inhibitory effect at IC50 of about 5 μM. These findings strongly suggested that integrin contributed to the malignancy of GBM cells. Furthermore, RNA was extracted from GBM cells treated with this drug, and transcriptome analysis was performed. As a result, we clarified a new signal transduction mechanism and multiple downstream pathways by integrin activation in GBM cells.

Free Research Field

創薬科学, がん生物学, 細胞生物学, 生化学

Academic Significance and Societal Importance of the Research Achievements

GBMは難治性希少疾患であり、有効な治療法が存在していないことから、治療法の開発に繋がる基礎研究の発展が求められている。本研究において開発した新規インテグリン阻害薬は正常細胞に効きにくく、かつ目的とするGBM細胞に効果的であった。今後、この作用機序が明らかになることで、GBM病態に対する新たな治療戦略に発展する可能性が大きいことが示唆された。