To clarify the role of USP45 in Epithelial-mesenchymal transition in bone

• Project/Area Number: 25861771
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hokkaido University
• Principal Investigator: Tanaka Soichi 北海道大学, 大学病院, 助教 (20548200)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 上皮間葉転換 / USP45 / EMT / 脱ユビキチン化酵素 / 骨微少環境 / ゾレドロン酸

Outline of Final Research Achievements

Clinical study has shown that breast cancer patients are improved overall survival by Bisphosphonate (ZOL). We investigated whether ZOL is involved in Epithelial-mesenchymal transition (EMT) in bone. We showed bone environment promotes EMT in breast cancer cells. Moreover, ZOL inhibits EMT in bone via stimulation of EMT inducing factor Snail degradation by preventing its de-ubiquitination by USP45, leading to the suppression of secondary metastases from bone.