Comprehensive analysis of the mechanisms underlying tumorigenesis of alveolar soft part sarcoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09623
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tottori University
• Principal Investigator: ISHIGURO Naoko 鳥取大学, 医学部, 助教 (50346350)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 胞巣状軟部肉腫 / ASPL-TFE3 / 融合遺伝子 / 腫瘍特異的転写制御

Outline of Final Research Achievements

The ASPL-TFE3 fusion oncogene, functioning as an aberrant transcription factor, contributes to the development and progression of alveolar soft part sarcoma by inducing inappropriate upregulation of target genes. To elucidate the underlying molecular mechanisms of tumorigenesis, we comprehensively investigated the transcriptional target of ASPL-TFE3 using ChIP-seq analysis. We identified metabolic factors, angiogenesis factors, signal transduction factors, and growth factors as candidate downstream targets of ASPL-TFE3. Moreover, our results suggest that upregulation of these target genes resulted in promotion of proliferation, migration and invasion of tumor cells.

Free Research Field

腫瘍生物学、整形外科

Academic Significance and Societal Importance of the Research Achievements

ASPL-TFE3融合遺伝子は胞巣状軟部肉腫の発症・進展において重要な役割を果たすことから、本融合遺伝子の機能解析は胞巣状軟部肉腫の分子病態を理解する上で重要な手がかりになると考えられる。また一般に、転写制御因子としてはたらく融合遺伝子は、下流の転写標的遺伝子群の発現異常を引き起こすことで腫瘍の発症に寄与しており、その標的遺伝子の同定は新たな分子標的治療法の開発に展開する分子基盤の確立につながると期待される。