Relationship between FH tumor-suppressor gene and aerobic glycolysis (Warburg effect)

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Dokkyo Medical University
• Principal Investigator: Kamai Takao 獨協医科大学, 医学部, 教授 (80316562)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 腎細胞癌 / HLRCC / Akt / Nrf2 / aerobic glycolysis

Outline of Final Research Achievements

The main findings of the present study were as follows: 1) A higher standard glucose uptake value (SUVmax) on 18F-FDG-PET was correlated with higher expression of phosphorylated Akt(Ser-473) in the primary tumor. A higher SUVmax and increased expression of phosphorylated Akt(Ser-473) was associated with a higher pT stage,and metastasis, as well as shorter overall survival in RCC patients. 2) Targeted next-generation sequencing revealed that fumarate hydratase (fumarase, FH) mutation and loss of the second allele were completely identical between blood and tumor samples in Hereditary Leiomyomatosis and Renal Cell Cancer（HLRCC）cancer patients. Furthermore, surgically resected samples showed high expression of phosphorylated Akt(Ser-473) as well as nuclear factor E2-related factor 2 (Nrf2), suggesting that FH mutation plays a direct role in a metabolic shift to aerobic glycolysis), and increased an anti-oxidant response phenotype in HLRCC-associated kidney cancer.

Free Research Field

泌尿器科