Study on the tumor suppressor Hippo pathway and RASSF proteins

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293061
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hata Yutaka 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (80313237)
• Co-Investigator(Renkei-kenkyūsha): Iwasa Hiroaki 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (70582188) ; Maruyama Junichi 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (30723639)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: シグナル伝達 / 腫瘍抑制

Outline of Final Research Achievements

YAP1 and TAZ, targets of the tumor suppressor Hippo pathway, regulate cell proliferation and differentiation. Hyperactive YAP1 and TAZ provide cancer cells with malignant properties and shorten disease-free survival. On the other hands, YAP1 and TAZ play essential roles in tissue stem cells and their activities are crucial for tissue homeostasis. Thereby, YAP1 and TAZ inhibitors and activators are useful in cancer therapy and regenerative medicine, respectively. We established cell-based assays to search for YAP1 and TAZ inhibitors and activators, and performed the chemical compound screening. We characterized the obtained candidates, validated the assays and evaluated their therapeutic potentiality. We also studied RASSF6, a tumor suppressor that is closely related to the Hippo pathway. We revealed that RASSF6 blocks MDM2-mediated degradation of p53. Ras signaling strengthens the binding of RASSF6 to MDM2. In this way, RASSF6 functions as a tumor suppressor against oncogenic Ras.

Free Research Field

医化学