Role of p53-inducible glutamine regulator GLS2 in the pathogenesis of NASH-HCC

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14375
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Chiba University
• Principal Investigator: TANAKA Tomoaki 千葉大学, 大学院医学研究院, 教授 (50447299)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: NASH / 生活習慣病 / 肝臓がん / グルタミン代謝 / がん抑制遺伝子

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