Elucidating the mechanisms of tissue homeostasis by epithelial clock machinery

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21501
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Kyoto University
• Principal Investigator: Enomoto Masato 京都大学, 生命科学研究科, 助教 (00596174)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: がん / シグナル伝達 / 概日時計 / 上皮 / ショウジョウバエ

Outline of Final Research Achievements

Although cancers progress by accumulation of genetic alterations, the mechanism by which oncogenic cells collectively initiate tumorigenesis in vivo is still poorly understood. In this research, using Drosophila epithelium I conducted a genetic screen of mutants that cause tumor progression of oncogenic cell populations with Src activation. Through this genetic screen, I isolated mutants of circadian clock gene for promoting tumor overgrowth of Src-activated cell clones. From genetic analyses, mutation of circadian clock gene in Src-activated cell clones induces Akt signaling activation, which causes tumorigenesis of these oncogenic clones. These genetic findings show a genetic link between oncogenic alterations and circadian clock and suggest that dysregulation of epithelial clock machinery initiates tumor progression.

Free Research Field

細胞生物学、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究はショウジョウバエをモデルとして、概日時計を制御する遺伝子の異常ががんの発生を誘発する可能性を生体レベルで示したものである。このことは、生体内の個々の組織がもつ適切な概日時計リズムががん化の抑制に重要であることを示唆している。将来的に本現象を哺乳類において解析しその普遍性を明らかにすることで、体内時計の調節を基盤とした新たながん制御やがん治療法の確立が期待される。