The role of Wnt5a and the interaction of canonical and noncanonical Wnt pathway in osteosarcoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16615
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Shinshu University
• Principal Investigator: Sasaki Jun 信州大学, 医学部附属病院, 特任助教 (20814122)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 骨肉腫 / Wnt経路 / Wnt5a / LRP5 / LRP6

Outline of Final Research Achievements

Wnt ligands regulate bone formation through beta-catenin-dependent canonical and　-independent noncanonical Wnt signaling pathways. The two signaling pathways cooperate with each other during osteoblastogenesis, although noncanonical Wnt5a antagonizes the canonical Wnt pathway in various types of cells. Wnt5a-induced noncanonical signals enhance the canonical Wnt pathway through up-regulation of Lrp5/6 to achieve proper bone formation. This study suggested that Wnt5a has the similar function in the human osteosarcoma cell (malignant bone tumor). Furthermore, this study suggested that the function of Wnt5a correlates with clinical outcome of osteosarcoma.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

本研究では、小児に好発する悪性骨腫瘍である骨肉腫における、Wnt5aの新たな作用の存在を検証した。非古典経路のWnt5aは、古典経路に受容な共受容体であるLRP5/6の発現を調節していることが示唆された。そして臨床検体におけるLRP5/6やさらに下流のβカテニンの発現と臨床成績とには関連が認められた。この経路は骨肉腫の新たな治療標的となる可能性があると考えられた。