Explore the irreversible check point from normal to malignant transformation of the cells by changing in the balance of the expression levels of the EP prostanoid receptor subtypes.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: The University of Tokushima
• Principal Investigator: FUJINO Hiromichi 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (40401004)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん発症メカニズムの解明

Outline of Final Research Achievements

To explore the irreversible check point from normal to cancer malignant transformation of the cells, changing in the expression balances of the EP2 and EP4 prostanoid receptors were examined in terms of their functions of the cancer-related cellular signaling pathways. In 2020, the decreasing in the expression level of EP2 receptors hence sustaining the EP4 receptor-mediated signaling were suggested to be found as one of the reasons for cancer malignancy. In 2021, the levels of the expression balances of EP2 and EP4 receptors were confirmed to be important since each receptor has its own specific/independent functions to regulate the cellular functions including cancer cells. In 2022, altering the glycometabolisms evoked by the sustained activation of the EP4 receptors were suggested to be one of the irreversible check point to cancer malignant transformation.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

受容体を２つ同時にノックアウトさせた研究は散見するが、２つの受容体発現量バランス変化に着目した研究は存在しない。EP4受容体の過活性化は、がん発症の重要な要因である可能性が示されたが、それだけでは不可逆的に進行するがんの悪性化を説明できない。本研究で、その不可逆性を決定づけるEP2受容体の減少を提案し、その増悪機構の一端を明らかにした学術的意義は大きいと考える。またこのメカニズムをベースとし、不可逆性を獲得するその起点を超えさせないことができれば、悪性化抑制だけではなく、可逆的に正常状態近くまで引き戻せる可能性が考えられ、全く新しいがん治療法を提案できるその社会的意義は大きいと考える。