Elucidation of the molecular mechanism of the malignant transformation of cancer with the Wnt5a signal and development of the molecular target medicine

2015 Fiscal Year Final Research Report

• Project/Area Number: 25250018
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: Kikuchi Akira 大阪大学, 医学(系)研究科(研究院), 教授 (10204827)
• Co-Investigator(Kenkyū-buntansha): FUMOTO KATSUMI 大阪大学, 大学院医学系研究科, 助教 (40467783) ; MATSUMOTO SHINJI 大阪大学, 大学院医学系研究科, 特任助教 (20572324)
• Project Period (FY): 2013-10-21 – 2016-03-31
• Keywords: Wnt5a / Wntシグナル / がん / 炎症 / エンドサイトーシス / サイトカイン / 炎症性腸疾患

Outline of Final Research Achievements

This project focused on the molecular actions of Wnt5a, a representative ligand for the β-catenin-independent pathway, which has been implicated in various adult diseases including cancer. We obtained following results. 1) In polarized epithelial cells, Wnt5a and its receptor were trafficked to the basolateral region to regulate the formation of inner cavity of cysts by promoting cell-extracellular matrix attachment. 2) Wnt5a-dependent cancer cells invasion was depend on receptor-mediated endocytosis, but not and Wnt5a-dependent cancer cells proliferation was. 3) We developed a high throughput screening system to detect Wnt5a-dependent signal effectively and identified two chemical compounds for the inhibition of Wnt5a signaling. 4) Wnt5a signal enhanced interleukin-12 production in dendritic cells to promote Th1 immune-response in colorectal inflammation. These results suggest that Wnt5a signaling could be a novel therapeutic target for cancer and inflammation disease.

Free Research Field

生化学