Analysis of Changes in SUMO-2/3 Modification during Breast Cancer Progression and Metastasis
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- 作者：Divya Subramonian ; Sarita Raghunayakula ; Jesper V. Olsen ; Karen A. Beningo ; Wulf Paschen ; Xiang-Dong Zhang
- 刊名：Journal of Proteome Research
- 出版年：2014
- 出版时间：September 5, 2014
- 年：2014
- 卷：13
- 期：9
- 页码：3905-3918
- 全文大小：671K
- ISSN：1535-3907
文摘
SUMOylation is an essential posttranslational modification and regulates many cellular processes. Dysregulation of SUMOylation 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鈥損eptide 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 SUMOylation on breast cancer progression and metastasis.