Analysis of the specific target signaling of glioma stem cells by the integrated phospho-glycomics

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14383
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kumamoto University
• Principal Investigator: Araki Norie 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: cancer stem cells / glioma / proteomics

Outline of Final Research Achievements

Glioma stem cells (GSCs) are considered responsible for the glioma malignancy. To understand the molecular mechanism, we established GSCs having potential to form glioblastoma, and subjected to transcriptome/proteome analyses coupled with phospho-glyco proteomics. The results showed that GSCs had the higher level of O-GlcNAcylation (OG) pathways. Suppressions of OG synthesis resulted in global decreases of OG proteins (OGPs), with the downregulation of GSC proliferations. To identify GSC-associated-OGPs, GSCs were metabolically labeled with GlcNAz and analyzed by LC-MS/MS searching with Ser/Thr phospho-/O-GlcNac-modified peptides. Among 4336 identified-proteins, we focused 23 OGPs possessing the phospho-transition/conversion sites. They involve in DNA-binding, the chromatin remodeling, transcriptions, and neural cell differentiations. The transition/conversion of O-GlcNAcylation to phosphorylation in nuclear factors may be an important mechanism for GSC differentiation to glioma cells.

Free Research Field

腫瘍生化学