title: Analysis of changes in SUMO-2/3 modification during breast cancer progression and metastasis.
abstract: 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-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 SUMOylation on breast cancer progression and metastasis.
authors: Department of Biological Sciences, Wayne State University , 5047 Gullen Mall, Detroit, Michigan 48202, United States.
authors: Divya
authors: D
authors: Subramonian
authors: Sarita
authors: S
authors: Raghunayakula
authors: Jesper V
authors: JV
authors: Olsen
authors: Karen A
authors: KA
authors: Beningo
authors: Wulf
authors: W
authors: Paschen
authors: Xiang-Dong
authors: XD
authors: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004330:Drosophila; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D009385:Neoplastic Processes; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D016415:Sequence Alignment; D025841:Small Ubiquitin-Related Modifier Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins