Analysis of Changes in SUMO-2/3 Modification during Breast Cancer Progression and Metastasis

被引：27

作者：

Subramonian, Divya ^{[1
]}

Raghunayakula, Sarita ^{[1
]}

Olsen, Jesper V. ^{[2
]}

Beningo, Karen A. ^{[1
]}

Paschen, Wulf ^{[3
]}

Zhang, Xiang-Dong ^{[1
]}

机构：

[1] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA

[2] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Dept Prote, DK-2200 Copenhagen N, Denmark

[3] Duke Univ, Dept Anesthesiol, Med Ctr, Durham, NC 27710 USA

来源：

JOURNAL OF PROTEOME RESEARCH | 2014年 / 13卷 / 09期

关键词：

breast cancer; metastasis; quantitative mass spectrometry; SILAC; small ubiquitin-like modifiers; posttranslational modification; cell migration; glycolysis; inflammation; PML; UBIQUITIN-LIKE PROTEIN; INHIBITORY FACTOR MIF; COVALENT MODIFICATION; TARGET PROTEINS; SUMOYLATION; PML; CONJUGATION; EXPRESSION; COMPLEX; GTPASE;

D O I：

10.1021/pr500119a

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3905 / 3918

页数：14

共 72 条

[1] Small Ubiquitin-related Modifier (SUMO)-1 Promotes Glycolysis in Hypoxia [J].