Next-generation proteomics to reveal the mechanism for malignant transformation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19606
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Kyushu University
• Principal Investigator: Masaki Matsumoto 九州大学, 生体防御医学研究所, 准教授 (60380531)
• Research Collaborator: Nakayama Keiichi
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: プロテオミクス / 代謝 / がん

Outline of Final Research Achievements

In this study, we established an in vitro model for malignant transformation from oncogene-induced pre-cancerous state cell line. In order to reveal the molecular basis of malignant transformation, the expression level of metabolic enzymes in these cell lines was quantified by our originally developed next-generation proteomics, iMPAQT. We found that glutamine metabolism is significantly altered during malignant transformation and PPAT which transfers nitrogen to 5-phosphoribosyl-1-pyrophosphate (PRPP), a precursor in nucleotide biosynthesis, from glutamine, acts as a key enzyme in cancer specific glutamine metabolism. We also demonstrated that attenuation of PPAT induces the reduction in the tumor size.

Free Research Field

プロテオミクス

Academic Significance and Societal Importance of the Research Achievements

本研究によってがんの悪性進展過程においてグルタミン代謝経路が核酸合成に偏重してシフトしていることを見出した。このがん特有の代謝シフトの原因であるPPATの発現抑制によって腫瘍形成を減弱させることができたことから、この酵素が抗がん剤の有効なターゲットとなり得ることが示唆された。また、代謝酵素の一斉定量法を確立したことで、広範な疾患の分子機構を代謝経路の変化として捉えることが可能となった。