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

Research Project

Project/Area Number 18K16615
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionShinshu 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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords骨肉腫 / Wnt経路 / Wnt5a / LRP5 / LRP6 / 古典経路 / 非古典経路
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.

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。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Clinical outcome of osteosarcoma and its correlation with programmed death-ligand 1 and T cell activation markers2019

    • Author(s)
      Yoshida Kazushige、Okamoto Masanori、Sasaki Jun、Kuroda Chika、Ishida Haruka、Ueda Katsuya、Okano Satomi、Ideta Hirokazu、Kamanaka Takayuki、Sobajima Atsushi、Takizawa Takashi、Kito Munehisa、Aoki Kaoru、Uemura Takeshi、Haniu Hisao、Kato Hiroyuki、Saito Naoto
    • Journal Title

      OncoTargets and Therapy

      Volume: Volume 12 Pages: 2513-2518

    • DOI

      10.2147/ott.s198421

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2021-02-19  

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