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2020 Fiscal Year Final Research Report

The expression of FOXM1 under acidic microenvironment in sarcoma and development of the treatment

Research Project

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Project/Area Number 19K16801
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionThe University of Tokushima

Principal Investigator

TOKI Shunichi  徳島大学, 病院, 助教 (60837194)

Project Period (FY) 2019-04-01 – 2021-03-31
KeywordsFOXM1 / 肉腫 / 酸性環境 / チオストレプトン / 細胞周期 / 細胞増殖 / 遊走
Outline of Final Research Achievements

In this study, we found high expression of FOXM1, a transcription factor that activates genes related to cell cycle and proliferation and is involved in multiple oncogenic signaling pathway, including epithelial-mesenchymal transition, cell invasion, angiogenesis, and DNA damage repair response, in soft tissue sarcomas exposed to acidic microenvironments. In addition, comprehensive analysis comparing between acidic and neutral microenvironment showed that the expression of FOXM1, PLK1, CCNB2, CDC25B, CENPF, and AURKB was markedly upregulated in acidic microenvironment. Furthermore, FOXM1 knockdown or thiostrepton treatment of liposarcoma cell lines showed pronounced suppression of cell proliferation, migration, and invasion in especially acidic microenvironment cells.

Free Research Field

骨・軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

希少がんである肉腫に対する治療薬開発は、少ない症例数やリソース、多様な組織型、企業の採算性などの理由から、今日のがん医療の重要な課題である。FOXM1は一般に悪性腫瘍において高発現で、正常の組織では一部の組織を除いてほとんど発現がなく、またその発現が予後に関与するとされている。本研究成果により、FOXM1は特に脂肪肉腫における選択的治療の標的となり得ることが示された。また、本研究のデータでも粘液線維肉腫や血管肉腫などでFOXM1高発現が認められたように、FOXM1抑制因子(がん抑制遺伝子)TP53遺伝子異常を有する症例が多い軟部肉腫においては、FOXM1標的治療法の臨床応用が強く期待される。

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Published: 2022-01-27  

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