The role of enhancer reprogramming in MIT/TFE family tumor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07702
• 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: Japanese Foundation for Cancer Research
• Principal Investigator: TANAKA Miwa 公益財団法人がん研究会, がん研究所 がんエピゲノムプロジェクト, 主任研究員 (70345883)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 骨軟部腫瘍 / 融合遺伝子 / スーパーエンハンサー / 血管新生 / MIT/TFEファミリー / マウスモデル / マイクロデバイス / ASPL-TFE3

Outline of Final Research Achievements

Alveolar soft part sarcoma (ASPS) occurs mostly in young adults with frequent hematogenous metastasis even at the initial diagnosis. This goal is to clarify the specific interaction between ASPL-TFE3 (AT3) and super-enhancer (SE), especially the angiogenesis mechanism that is characteristic of ASPS, and to develop therapeutics targeting molecules responsible for carcinogenesis and angiogenesis.
We identified SEs essential for AT3-controlled tumorigenesis and their target genes by CRISPR epigenome screening. Moreover, we used our mouse models and microfluidic devices to determine their role in the development and angiogenesis of ASPS.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

胞巣状軟部肉腫(ASPS)の生体内での維持と転移には、腫瘍と血管の密接な相互作用が不可欠であるが、既存の抗がん剤の効果が乏しいことから、ASPSでの血管形成機構の解明が治療開発に最重要であると考えた。本研究課題の成果により治療標的を見出した。現在は創薬シーズの獲得に向けて研究を推進している。