Imperial College London
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DrLeandroCastellano

Faculty of Medicine, Department of Surgery & Cancer

Visiting Reader
 
 
 
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Contact

 

+44 (0)20 7594 2822l.castellano Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Britton:2014:10.1371/journal.pone.0090948,
author = {Britton, D and Zen, Y and Quaglia, A and Selzer, S and Mitra, V and Loessner, C and Jung, S and Boehm, G and Schmid, P and Prefot, P and Hoehle, C and Koncarevic, S and Gee, J and Nicholson, R and Ward, M and Castellano, L and Stebbing, J and Zucht, HD and Sarker, D and Heaton, N and Pike, I},
doi = {10.1371/journal.pone.0090948},
journal = {PLOS One},
title = {Quantification of Pancreatic Cancer Proteome and Phosphorylome: Indicates Molecular Events Likely Contributing to Cancer and Activity of Drug Targets},
url = {http://dx.doi.org/10.1371/journal.pone.0090948},
volume = {9},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Objective: LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events thatlead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signalingpathways and drug targets in pancreatic cancer tissue for clinical application.Methods: Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductaladenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strongcation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides usingIMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevantbiological events from the complex dataset.Results: Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumortissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority werenew candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 uniquephosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rhoguanine nucleotide exchange factors & MRCKa) and formation of focal adhesions. Activator phosphorylation sites on FYN,AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated ($2 fold) in different cases highlightingtheir predictive power.Conclusion: Here we provided critical information enabling us to identify the common and unique molecular events likelycontributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for anindividual case.
AU  - Britton,D
AU  - Zen,Y
AU  - Quaglia,A
AU  - Selzer,S
AU  - Mitra,V
AU  - Loessner,C
AU  - Jung,S
AU  - Boehm,G
AU  - Schmid,P
AU  - Prefot,P
AU  - Hoehle,C
AU  - Koncarevic,S
AU  - Gee,J
AU  - Nicholson,R
AU  - Ward,M
AU  - Castellano,L
AU  - Stebbing,J
AU  - Zucht,HD
AU  - Sarker,D
AU  - Heaton,N
AU  - Pike,I
DO  - 10.1371/journal.pone.0090948
PY  - 2014///
SN  - 1932-6203
TI  - Quantification of Pancreatic Cancer Proteome and Phosphorylome: Indicates Molecular Events Likely Contributing to Cancer and Activity of Drug Targets
T2  - PLOS One
UR  - http://dx.doi.org/10.1371/journal.pone.0090948
UR  - http://hdl.handle.net/10044/1/29189
VL  - 9
ER  -
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