Application of dopamine receptor antagonist inhibiting WNT-YAP/TAZ pathway for colon cancer treatment

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18457
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Iwate Medical University
• Principal Investigator: Oku Yusuke 岩手医科大学, 薬学部, 講師 (50626843)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: YAP/TAZ / がん分子標的薬

Outline of Final Research Achievements

We originally identified WNT-beta catenin signal inhibitors including pimozide, a dopamine receptor antagonist. In this study, we found that these WNT-beta catenin inhibitors inhibits the nuclear translocation of transcriptional co-activator YAP/TAZ by WNT. Nuclear translocation of YAP/TAZ is facilitated by lysophosphatidic acid (LAP).However, WNT-beta catenin inhibitors including pimozide did not inihbit LAP-mediated nuclear translocation of YAP/TAZ. These results suggested that WNT-beta-catenin inhibitors which we identified preferentially inhibits WNT-mediated nuclear translocation of YAP/TAZ.

Free Research Field

腫瘍生物学