期刊
JOURNAL OF PROTEOME RESEARCH
卷 13, 期 9, 页码 3905-3918出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr500119a
关键词
breast cancer; metastasis; quantitative mass spectrometry; SILAC; small ubiquitin-like modifiers; posttranslational modification; cell migration; glycolysis; inflammation; PML
资金
- WSU [142146]
- American Cancer Society Institutional Research Grant [11-053-01-IRG]
SLTMOylation is an essential posttranslational modification and regulates many cellular processes. Dysregulation of SLTMOylation plays a critical role in metastasis, yet how its perturbation affects this lethal process of cancer is not well understood. We found that SUMO-2/3 modification is greatly up-regulated in metastatic breast cancer cells compared with nonmetastatic control cells. To identify proteins differentially modified by SUMO-2/3 between metastatic and nonmetastatic cells, we established a method in which endogenous SUMO-2/3 conjugates are labeled by stable isotope labeling by amino acids in cell culture (SILAC), immunopurified by SUMO-2/3 monoclonal antibodies and epitope peptide elution, and analyzed by quantitative mass spectrometry. We identified 66 putative SUMO-2/3-conjugated proteins, of which 15 proteins show a significant increase/decrease in SUMO-2/3 modification in metastatic cells. Targets with altered SUMOylation are involved in cell cycle, migration, inflammation, glycolysis, gene expression, and SUMO/ubiquitin pathways, suggesting that perturbations of SUMO-2/3 modification might contribute to metastasis by affecting these processes. Consistent with this, up-regulation of PML SUMO-2/3 modification corresponds to an increased number of PML nuclear bodies (PML-NBs) in metastatic cells, whereas up-regulation of global SUMO-2/3 modification promotes 3D cell migration. Our findings provide a foundation for further investigating the effects of SLTMOylation on breast cancer progression and metastasis.
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