WT1 controls metabolism in hematopoietic malignancies

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08732
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Osaka University
• Principal Investigator: Oji Yusuke 大阪大学, 大学院医学系研究科, 教授 (20294100)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: WT1

Outline of Final Research Achievements

WT1 protein directly binds to metabolic enzymes and enhances their enzymatic activity. In this study, 1) WT1-derived peptide that has a sequence of the biding sequence to the metabolic enzymes induces cell death in leukemic cells, and 2) the metabolically stable D-form WT1 peptide, showed more potent antitumor effects than the native peptide. 3) WT1 peptide showed antitumor activity in leukemic cells and various solid malignant tumors expressing WT1. These results indicate that the PPIs between WT1 and metabolic enzymes play essential roles in the survival of leukemia and many other cancer types and that they can be targets for novel molecular-targeted therapies.

Free Research Field

がん生物学

Academic Significance and Societal Importance of the Research Achievements

本課題ではWT1と代謝酵素のPPIが白血病および膵がんや悪性神経膠腫において生存に重要な役割を果たしており、このWT1と代謝酵素のPPIが新たな分子標的のターゲットになりうることを示した。これはこれまで核タンパクとして転写やスプライシング調節に関与すると考えられてきたWT1タンパクの新たながん遺伝子機能を明らかにしたものである。さらにWT1タンパクと代謝酵素のPPIが分子標的治療の新たなターゲットとなりうることは、腫瘍特異的で広い癌種に対して適応可能な新規メカニズムの分子標的治療の可能性を示すものである。