A treatment strategy to target mitochondria-specific Hsp90 chaperones

2015 Fiscal Year Final Research Report

• Project/Area Number: 25830075
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YOSHIDA Soichiro 東京医科歯科大学, 医学部附属病院, 助教 (80383280)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 尿路上皮癌 / 分子シャペロン / ミトコンドリア

Outline of Final Research Achievements

TRAP1, a homologue of HSP90, are abundantly expressed in mitochondria.
We investigated the biological and prognostic role of TRAP1 expression in upper urinary tract urothelial carcinoma (UTUC). In 5637 cells, knockdown of endogenous TRAP1 potentiated cell invasiveness, which is attenuated by a ROS inhibitor. In addition, exogenous expression of TRAP1 hampered in vitro invasion of 5637 cells. We further evaluated TRAP1 expression in UTUC surgical specimens and its association with cancer-specific survival (CSS). Lower TRAP1 expression was an independent predictor of shorter CSS, along with histological grade and lymph node involvement. The 5-year CSS rates were 52% for patients with lower TRAP1 expression compared to 95% for those with higher TRAP1 expression. Taken together, impaired TRAP1 expression is associated with increased invasive potential via modulating ROS and unfavorable prognosis in UTUC.

Free Research Field

泌尿器科