Elucidation of the upstream regulatory mechanism of UCHL1-HIF-1 pathway in cancer microenvironment and development of the pathway for enhancing radiosensitivity

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06337
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: Goto Yoko 京都大学, 医学研究科, 助教 (60755651)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: 放射線治療 / 低酸素 / HIF-1 / UCHL1

Outline of Final Research Achievements

Cancer cells under hypoxic environment activate hypoxia-inducible factor (HIF-1), resulting in enhancing malignant phenotype. We identified UCHL1 as a novel upstream activator of HIF-1 through an original genetic screening strategy. Furthermore, we revealed that the UCHL1-HIF-1 pathway is responsible for distant metastasis of cancer and leads to poor prognosis of cancer patients. In this study, we aimed to elucidate the upstream regulatory mechanisms of the UCHL1-HIF-1 pathway. In addition, we elucidated that UCHL1-HIF-1 pathway contribute to radioresistance of cancer cells via metabolic reprogramming and proved a rational basis for targeting this pathway for radiosensitization.

Free Research Field

放射線生物学