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

Research Project

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
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	放射線治療 / 低酸素 / HIF-1 / UCHL1 / 悪性腫瘍
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.

Report

(3 results)