Acid adaptation of cells via lysosomal exocytosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kyoto University (2022-2023); Osaka University (2020-2021)
• Principal Investigator: Funato Yosuke 京都大学, 工学研究科, 准教授 (60505775)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: PRL / がん悪性化 / 酸性環境適応 / lysosomal exocytosis

Outline of Final Research Achievements

In this study, we investigated the response of cells against environmental pH, typically focusing on the mechanism of acid adaptation of cancer cells via PRL-mediated activation of lysosomal exocytosis and its importance in cancer malignancy. As a result, we found that activation of lysosomal exocytosis is necessary for cancer cells to adapt to acidic environments upon PRL overexpression and for PRL-induced tumorigenesis in mice, and we also identified several new molecules involved in this PRL-dependent adaptation to acidic environments.

Free Research Field

医化学関連

Academic Significance and Societal Importance of the Research Achievements

腫瘍組織が酸性化していることは古くから知られているが、同じ「腫瘍内微小環境」として知られる低酸素などと比べその研究は大きく遅れている。本研究により細胞のpH応答性についての理解が進み酸性環境適応の機構解明に向けての取り組みが促進されることで、新たながん悪性化機構の理解や新規診断・治療法の開発へとつながる可能性が考えられる。