Analysis of regulatory mechanisms of DKK1 gene expression and its role in the cancer microenvironment in refractory cancers

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16330
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Osaka University
• Principal Investigator: Sada Ryota 大阪大学, 大学院医学系研究科, 助教 (60869783)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: DKK1 / CKAP4 / FOXM1 / 膵がん / 肝がん / 肺がん

Outline of Final Research Achievements

We have previously elucidated the mechanism of cell proliferation mediated by DKK1-CKAP4 signaling in various cancers. In this study, we comprehensively analyzed the genes expressed downstream of DKK1-CKAP4 signaling in pancreatic cancer cell line S2-CP8 and focused to the transcription factor FOXM1, which promotes DKK1 expression in a positive feedback mechanism to enhance tumor cell growth of pancreatic and esophageal squamous cell carcinoma cells. We elucidated that co-expression of DKK1 and FOXM1 is an independent poor prognostic factor in pancreatic cancer and esophageal squamous cell carcinoma, and that DKK1-CKAP4 FOXM1 signaling is a potential therapeutic target. We have published our findings in a paper.

Free Research Field

molecular biology

Academic Significance and Societal Importance of the Research Achievements

今回の私共の研究成果の学術的意義は、難治性がんにおけるWntシグナルと独立したDKK1過剰発現の分子機構を明らかにしたことである。
また私共が開発した抗CKAP4抗体が、DKK1-CKAP4-FOXM1シグナルを阻害することで、in vivoにおける腫瘍増殖抑制を示すことを明らかにした。難治性がんの分子病態の理解と、将来の新規治療戦略の開発につながることが期待される点で、今回の私共の研究成果の社会的意義がある。