Elucidation of the molecular mechanisms by which DPP-4 plays a role in the development and metastasis of malignant tumors

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16214
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: TAKAGAKI Yuta 金沢医科大学, 医学部, 助教 (50759123)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖尿病 / DPP-4 / 癌

Outline of Final Research Achievements

In vitro, DPP-4 inhibitor treatment induced EMT program by activating mTOR in a CXCL12/CXCR4 signaling-dependent manner, and in vivo, CXCR4 inhibitor treatment reduced tumor size and suppressed metastasis. In addition, DPP-4 knockdown breast cancer cells acquired resistance to doxorubicin through induction of the EMT program. Using surgical specimens, we found that DPP-4 expression was increased and CXCR4 expression was decreased in Stage I breast cancer tissues, while DPP-4 expression was decreased and CXCR4 expression was increased in Stage IV breast cancer tissues.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

糖尿病患者は癌のリスクが上昇することが知られており、2倍以上リスクが増加する癌種もあり、糖尿病治療薬により発癌、病期進行を来す可能性に関しては十分な検討が必要である。本研究の結果は現在、その優れた血糖降下作用や低血糖リスクの少なさから、高齢者を含めた多くの患者に使用されている、DPP-4阻害薬の新たなリスクの可能性を明らかにすることで、より病態に応じた使い分けを行う指標となる。