Elucidation of the mechanism of vascular mimicry by Ror1-Rif signaling

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15504
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kobe University
• Principal Investigator: Kamizaki Koki 神戸大学, 医学研究科, 助教 (00883448)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Wnt5a-Ror1 / 肺腺がん / 浸潤 / 血管擬態

Outline of Final Research Achievements

Until now, the role of Wnt5a-Ror1 signaling in lung adenocarcinoma cells has been unknown. This study found that the small GTPase Rif regulates Wnt5a-Ror1 signaling and contributes to filopodia formation. We also found that suppression of Rif or Ror1 expression decreased lung adenocarcinoma cells' proliferation, invasion, and vascular mimicry. It was suggested that Ror1 signaling might be involved in extracellular matrix degradation during invasion and intercellular tension during vascular mimicry formation. This analysis indicates that Rif-Wnt5a-Ror1 signaling plays important roles in various functions of lung adenocarcinoma cells via filopodia formation.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまでがん細胞の浸潤には浸潤突起が重要であるという報告が多かったが、今回の解析結果から浸潤突起とは異なる突起構造である糸状突起も浸潤に重要であることが明らかとなった。また、糸状突起は浸潤だけでなく、生存や増殖、血管擬態にも重要であることがわかり、がん細胞の多様な機能制御を担う新たな突起構造として明らかにできた点で学術的意義は大きい。今後、糸状突起の多様な機能について詳細に解析することで、将来的に新規がん治療薬の創出に繋がることが期待されるため、社会的意義も十分に有する研究成果であると考える。