Daniel Liebler
Faculty Member
Last active: 2/15/2016

Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels.

Mertins P, Yang F, Liu T, Mani DR, Petyuk VA, Gillette MA, Clauser KR, Qiao JW, Gritsenko MA, Moore RJ, Levine DA, Townsend R, Erdmann-Gilmore P, Snider JE, Davies SR, Ruggles KV, Fenyo D, Kitchens RT, Li S, Olvera N, Dao F, Rodriguez H, Chan DW, Liebler D, White F, Rodland KD, Mills GB, Smith RD, Paulovich AG, Ellis M, Carr SA
Mol Cell Proteomics. 2014 13 (7): 1690-704

PMID: 24719451 · PMCID: PMC4083109 · DOI:10.1074/mcp.M113.036392

Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis.

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (15)

Animals Breast Neoplasms Cold Ischemia Female Gene Expression Profiling Humans Mice Mice, Inbred NOD Neoplasm Transplantation Ovarian Neoplasms Phosphoproteins Phosphorylation Proteome Proteomics Transplantation, Heterologous

Connections (1)

This publication is referenced by other Labnodes entities:

Links