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Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival
S. Al Shboul, OE. Curran, JA. Alfaro, F. Lickiss, E. Nita, J. Kowalski, F. Naji, R. Nenutil, KL. Ball, R. Krejcir, B. Vojtesek, TR. Hupp, PM. Brennan
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
BB/C511599/1
Biotechnology and Biological Sciences Research Council - United Kingdom
BB/J00751X/1
Biotechnology and Biological Sciences Research Council - United Kingdom
NLK
Directory of Open Access Journals
from 2018
Freely Accessible Science Journals
from 2018
PubMed Central
from 2018
ROAD: Directory of Open Access Scholarly Resources
from 2018
- MeSH
- Glioblastoma enzymology mortality pathology MeSH
- Coculture Techniques methods MeSH
- Humans MeSH
- Survival Rate MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells enzymology MeSH
- Brain Neoplasms enzymology mortality pathology MeSH
- Agammaglobulinaemia Tyrosine Kinase metabolism MeSH
- Proteome metabolism MeSH
- Proteomics methods MeSH
- Signal Transduction * MeSH
- SOXB1 Transcription Factors metabolism MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex vivo models to support therapeutic discovery. A "functional proteomics" screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been overlooked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton tyrosine kinase (BTK). We demonstrate that BTK is expressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells, and an unidentified cell population which is SOX2-negative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.
Cardiff University Hospital Cellular Pathology Cardiff UK
Department of Basic Medical Sciences Faculty of Medicine The Hashemite University Zarqa Jordan
Department of Neuropathology Western General Hospital Edinburgh UK
Institute of Genetics and Cancer University of Edinburgh Edinburgh UK
International Centre for Cancer Vaccine Science University of Gdansk Gdansk Poland
Pamgene International BV 's Hertogenbosch Netherlands
Research Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute Brno Czech Republic
Translational Neurosurgery Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK
References provided by Crossref.org
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