Abstract
We integrated LC-MS/MS-based and protein antibody array-based proteomics with genomics approaches to investigate the phosphoproteome and transcriptome of gastric cancer cell lines and endoscopic gastric biopsies from normal subjects and patients with benign gastritis or gastric cancer. More than 3,000 non-redundant phosphorylation sites in over 1,200 proteins were identified in gastric cancer cells. We correlated phosphoproteome data with transcriptome data sets and reported the expression of 41 protein kinases, 5 phosphatases and 65 phosphorylated mitochondrial proteins in gastric cancer cells. Transcriptional expression levels of 190 phosphorylated proteins were >2-fold higher in gastric cancer cells compared to normal stomach tissue. Pathway analysis demonstrated over-presentation of DNA damage response pathway and underscored critical roles of phosphorylated p53 in gastric cancer. This is the first study to comprehensively report the gastric cancer phosphoproteome. Integrative analysis of the phosphoproteome and transcriptome provided an expansive view of molecular signaling pathways in gastric cancer.
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Abbreviations
- RTK:
-
Receptor tyrosine kinase
- MS:
-
Mass spectrometry
- HPLC:
-
High-performance liquid chromatography
- FDR:
-
False discovery rate
- ERLIC:
-
Electrostatic repulsion-hydrophilic interaction chromatography
- SCX:
-
Strong cation exchange
- IMAC:
-
Immobilized metal ion affinity chromatography
- DDR:
-
DNA damage response
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Acknowledgments
This work is supported by the National Cancer Centre of Singapore Research Fund. This work is also supported by grants from the Ministry of Education (ARC: T206B3211 to SKS) and the Agency for Science, Technology and Research (BMRC: 07/1/22/19/531 to SKS) of Singapore.
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Guo, T., Lee, S.S., Ng, W.H. et al. Global molecular dysfunctions in gastric cancer revealed by an integrated analysis of the phosphoproteome and transcriptome. Cell. Mol. Life Sci. 68, 1983–2002 (2011). https://doi.org/10.1007/s00018-010-0545-x
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DOI: https://doi.org/10.1007/s00018-010-0545-x