Multimodal mechanisms of oncogenesis induced by HTLV-1

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03514
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kumamoto University
• Principal Investigator: Yasunaga Jun-ichirou 熊本大学, 大学院生命科学研究部(医), 教授 (40362404)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: HTLV-1 / ATL / HBZ

Outline of Final Research Achievements

HBZ plays important roles in the oncogenic mechanisms of ATL. HBZ acts as a bifunctional RNA with both coding and non-coding functions. I have reported that HBZ RNA and protein induce expression of the human TP73 gene by different mechanisms, promoting cancer metabolism and epigenetic alteration in ATL cells (Toyoda K, Yasunaga JI, et al. Blood Cancer Discov, 2023). Furthermore, a mechanism by which HBZ protein activates the TGF-beta pathway via interaction with hA3G was reported (Shichijo T, Yasunaga JI, et al. PNAS, 2024).

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

HTLV-1 bZIP factor RNA及びタンパク質による発がん機序を明らかにし、新規治療標的として乳酸トランスポーターMCT1、MCT4を同定した。またATL細胞の増殖、生存にTGF-beta経路の活性化が必須であることも見出し、TGF-beta阻害剤、Smad阻害剤がATL細胞に細胞死を誘導することから、TGF-beta/Smad経路も治療標的となることを証明した。これらの知見は、ATLに対する新規治療法の開発に繋がる。