Development research of molecular targeted therapy for oral cancer mediated by ubiquitin ligase inhibitor

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893166
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: SAKAUE TAISHI 広島大学, 大学病院, 歯科診療医 (00735160)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: 口腔癌 / インテグリン / ユビキチンリガーゼ

Outline of Final Research Achievements

It was revealed that HDM2 was the ubiquitin ligase which regulated the ubiquitination of integrin beta 8 by binding to EGF-like repeat domains in integrin beta 8 subunit leg. Treatment of oral squamous cell carcinoma cells with HDM2 E3 ligase inhibitor led to the enhancement of expression of integrin beta 8 protein. In addition, the enhancement of expression of HDM2 protein promoted cell motility of oral squamous cell carcinoma cells. These findings indicated that HDM2 might tightlyregulate the degradation of integrin beta 8 protein by ubiquitin-proteasome system, and participate in regulation of invasion and metastasis of oral cancer. Therefore, it is expected that molecular targeted therapy targeting HDM2 ubiquitin ligase has the potential to be the novel therapy for oral squamous cell carcinoma.

Free Research Field

外科系歯学