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

Philipp Mertins, Feng Yang, Tao Liu, D. R. Mani, Vladislav A. Petyuk, Michael A. Gillette, Karl R. Clauser, Jana W. Qiao, Marina A. Gritsenko, Ronald J. Moore, Douglas A. Levine, Reid Townsend, Petra Erdmann-Gilmore, Jacqueline E. Snider, Sherri R. Davies, Kelly V. Ruggles, David Fenyo, R. Thomas Kitchens, Shunqiang Li, Narciso OlveraFanny Dao, Henry Rodriguez, Daniel W. Chan, Daniel Liebler, Forest White, Karin D. Rodland, Gordon B. Mills, Richard D. Smith, Amanda G. Paulovich, Matthew Ellis, Steven A. Carr

    Research output: Contribution to journalArticlepeer-review

    177 Scopus citations

    Abstract

    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 tissuespecific 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.

    Original languageEnglish (US)
    Pages (from-to)1690-1704
    Number of pages15
    JournalMolecular and Cellular Proteomics
    Volume13
    Issue number7
    DOIs
    StatePublished - Jul 2014

    ASJC Scopus subject areas

    • Analytical Chemistry
    • Biochemistry
    • Molecular Biology

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