Targeting the factors integrating microenvironmental signals in cancer stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20843
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Fukasawa Kazuya 岐阜薬科大学, 薬学部, 助教 (70907443)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: グリオブラストーマ / がん幹細胞 / ERK5

Outline of Final Research Achievements

Glioma stem cells (GSC) promote the aggressiveness of glioblastoma (GBM), the most fatal brain tumor. ERK5 is a member of the MAPK family. In this study, we have demonstrated that the MEK5-ERK5-STAT3 pathway plays a critical role in sustaining the stemness and tumorigenicity of GSCs. Silencing ERK5 in GSCs suppressed their ability to self-renew and inhibited the malignant growth of GBM, accompanied by a decrease in STAT3 phosphorylation. Introducing STAT3 counteracted the effects of ERK5 silencing on GSC characteristics. Furthermore, the expression and signaling of ERK5 were associated with poor prognosis in GBM patients with high stem cell properties. Finally, pharmacological inhibition of ERK5 significantly reduced GSC self-renewal and GBM growth. Overall, these findings uncover the crucial involvement of the MEK5-ERK5-STAT3 pathway in sustaining GSC characteristics and promoting the malignant growth of GBM, highlighting it as a potential target for GSC-directed therapy.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の遂行により、ERK5がグリオーマ幹細胞の機能制御メカニズムに深く関連することを見出した。さらに、ERK5阻害剤が、グリオーマ幹細胞の機能を抑制させる働きがあることを実証した。近年、グリオーマだけでなく白血病、乳がんや前立腺がんなどにおいても、その病態とがん幹細胞特性に緊密な関連性があることが報告されている。本研究成果による、「グリオーマ幹細胞の機能調節機構の解明」により、 グリオーマを含む難治性がんに対する新規治療標的が明確になるだけでなく、がん幹細胞が関与する様々ながんに対する根本的治療法開発への展開が期待される。