Interdisciplinary Research for the Development of Cancer Metastasis Inhibitors with Low Toxicity: Development of Inhibitors by Affinity Tagging Method

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Hiroshima University
• Principal Investigator: Ishida Atsuhiko 広島大学, 統合生命科学研究科(総), 教授 (90212886)
• Co-Investigator(Kenkyū-buntansha): 根平 達夫 広島大学, 統合生命科学研究科(総), 准教授 (60321692) ; 平野 哲男 広島大学, 統合生命科学研究科(総), 助教 (50228805) ; 秋月 一駿 広島大学, 統合生命科学研究科(総), 助教 (50881299)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: プロテインホスファターゼ / 阻害剤 / 細胞毒性 / がん転移 / 有機合成

Outline of Final Research Achievements

A novel enzyme CaM kinase phosphatase (CaMKP, also known as PPM1F/POPX2), discovered by the applicants, has been shown in recent studies to be a key enzyme that regulates cancer cell migration and invasion. Inhibitors of this enzyme, which the applicants have already discovered, have low cytotoxicity and are expected to become cancer metastasis inhibitors with fewer side effects. Therefore, in this research project, we aim to develop CaMKP inhibitors with higher inhibitory specificity by applying the "affinity tag method," which was used to develop CaMKP-specific substrates, and to examine their effects on breast cancer cell migration and invasion in an assay system using cultured breast cancer cells. The objective of this study was to verify the effect of CaMKP inhibitors on the migration and invasion of breast cancer cells by using cultured breast cancer cells.

Free Research Field

生化学、酵素化学

Academic Significance and Societal Importance of the Research Achievements

CaMKPを標的としたがん転移抑制剤の開発は全くはじめての試みである。従来の抗がん剤のようにがん細胞に対する選択毒性を持つものではなく、浸潤・ 遊走のみを抑制し且つ細胞毒性が低いものを創製しようとするのが本研究の特徴である。我が国で発見された新奇酵素CaMKPが新たな分子標的として注目されつつある現在、独自の生化学的視点に基礎をおいた有効な特異的阻害剤の開発は喫緊の課題であり、その特異的阻害剤の医学的応用に道を拓く意義は大きい。