Ischemia in Tumors Induces Early and Sustained Phosphorylation Changes in Stress Kinase Pathways but Does Not Affect Global Protein Levels

被引：307

作者：

Mertins, Philipp ^{[1
]}

Yang, Feng ^{[2
]}

Liu, Tao ^{[2
]}

Mani, D. R. ^{[1
]}

Petyuk, Vladislav A. ^{[2
]}

Gillette, Michael A. ^{[1
]}

Clauser, Karl R. ^{[1
]}

Qiao, Jana W. ^{[1
]}

Gritsenko, Marina A. ^{[2
]}

Moore, Ronald J. ^{[2
]}

Levine, Douglas A. ^{[3
]}

Townsend, Reid ^{[4
]}

Erdmann-Gilmore, Petra ^{[4
]}

Snider, Jacqueline E. ^{[4
]}

Davies, Sherri R. ^{[4
]}

Ruggles, Kelly V. ^{[5
]}

Fenyo, David ^{[5
]}

Kitchens, R. Thomas ^{[4
]}

Li, Shunqiang ^{[4
]}

Olvera, Narciso ^{[3
]}

Dao, Fanny ^{[3
]}

Rodriguez, Henry ^{[6
]}

Chan, Daniel W. ^{[7
]}

Lieblera, Daniel ^{[8
]}

Whiteb, Forest ^{[9
]}

Rodland, Karin D. ^{[2
]}

Millsc, Gordon B. ^{[10
]}

Smith, Richard D. ^{[2
]}

Paulovich, Amanda G. ^{[11
]}

Ellis, Matthew ^{[4
]}

Carr, Steven A. ^{[1
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA

[4] Washington Univ, Dept Med, St Louis, MO 63110 USA

[5] NYU, Dept Biochem, Langone Med Ctr, New York, NY 10016 USA

[6] NCI, NIH, Bethesda, MD 20892 USA

[7] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA

[8] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA

[9] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[11] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

来源：

MOLECULAR & CELLULAR PROTEOMICS | 2014年 / 13卷 / 07期

基金：

美国国家卫生研究院;

关键词：

POSTTRANSLATIONAL MODIFICATIONS; BREAST; EXPRESSION; INDICATORS; FIXATION; TIME;

D O I：

10.1074/mcp.M113.036392

中图分类号：

Q5 [生物化学];

学科分类号：

070307 [化学生物学];

摘要：

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.

引用

页码：1690 / 1704

页数：15

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