Phosphoproteome analysis of colorectal cancer for understanding of tumor biology and its application to development of treatment

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670572
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: MINAMOTO Toshinari 金沢大学, がん進展制御研究所, 教授 (50239323)
• Co-Investigator(Renkei-kenkyūsha): SUGIYAMA Naoyuki 慶應義塾大学, 政策・メディア研究科, 特任講師 (50545704)
• Research Collaborator: DOMOTO Takahiro
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 大腸がん / 蛋白質リン酸化 / GSK3β

Outline of Final Research Achievements

The phosphoproteomic approach explored the putative biological mechanism by which glycogen synthase kinase (GSK)3β promotes colon cancer progression. Inhibition of GSK3β significantly modified the level of phosphorylation in a number of proteins in colon cancer cells. Integration of phosphoproteome and metabolome analysis for these proteins phosphorylated by GSK3β identified the enzyme A, a rate-limiting enzyme in glucose metabolism, which was preferentially phosphorylated by GSK3β in cancer cells. The results suggest that GSK3β promotes cancer progression by induction of aberrant glucose metabolism via phosphorylation-dependent inactivation of the enzyme A. In all, this study demonstrates that cancer treatment targeting GSK3β depends on modulation of cancer-specific profile of protein phosphorylation.

Free Research Field

医歯薬学