Role of tumor suppressor p53 for aiming obesity and NASH and search for therapeutic targets

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670438
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Chiba University
• Principal Investigator: TANAKA Tomoaki 千葉大学, 医学(系)研究科(研究院), 准教授 (50447299)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: がん抑制遺伝子 / NASH / 生活習慣 / ROS / エネルギー代謝 / メタボローム

Outline of Final Research Achievements

Recent epidemiologic evidence suggests that type 2 diabetes and obesity are at significantly higher risk for many types of cancer. In this context, p53 has been shown to control mitochondrial functions through regulation of ROS and cell metabolism, implicating its potential role in biologic links between diabetes and cancer. Here we have explored p53 targets to regulate cell metabolism using ChIP- and RNA-sequencing and identified GLS2, a key enzyme to convert glutamine to glutamate, thereby a regulator of glutathione synthesis and ATP production via TCA cycle. GLS2 overexpression inhibited cancer cell growth as well as invasion in both vitro and vivo, suggesting its potential role for tumor suppression. Thus, p53-GLS2 pathway may contribute to the common pathogenesis between life-style related diseases and cancer.

Free Research Field

医歯薬学