| Title | Multidimensional Proteomics Reveals a Role of UHRF2 in the Regulation of EpithelialMesenchymal Transition (EMT) |
| Authors | Lai, Mi Liang, Lizhu Chen, Jiwei Qiu, Naiqi Ge, Sai Ji, Shuhui Shi, Tieliu Zhen, Bei Liu, Mingwei Ding, Chen Wang, Yi Qin, Jun |
| Affiliation | Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing 102206, Peoples R China. Natl Ctr Prot Sci Beijing, Beijing 102206, Peoples R China. Natl Engn Res Ctr Prot Drugs, Beijing 102206, Peoples R China. East China Normal Univ, Coll Life Sci, Ctr Bioinformat & Computat Biol, Shanghai, Peoples R China. East China Normal Univ, Coll Life Sci, Inst Biomed Sci, Shanghai, Peoples R China. Peking Univ, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Canc Hosp & Inst,Dept Gastrointestinal Oncol, Beijing 100142, Peoples R China. Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Alkek Ctr Mol Discovery, Dept Mol & Cellular Biol, Houston, TX 77030 USA. |
| Keywords | Cancer Biology*,Cell adhesion*,EMT,Mass Spectrometry,Metastasis,TFRE,Transcription*,UHRF2,migration,profiling SPECTROMETRY-BASED PROTEOMICS HEMI-METHYLATED DNA RING FINGER DOMAINS CELL-CYCLE NETWORK SRA PROTEIN UHRF1 HISTONE H3 TAIL E-CADHERIN TRANSCRIPTION FACTORS UBIQUITIN-LIKE BREAST-CANCER |
| Issue Date | 2016 |
| Publisher | MOLECULAR & CELLULAR PROTEOMICS |
| Citation | MOLECULAR & CELLULAR PROTEOMICS.2016,15(7),2263-2278. |
| Abstract | UHRF1 is best known for its positive role in the maintenance of DNMT1-mediated DNA methylation and is implicated in a variety of tumor processes. In this paper, we provided evidence to demonstrate a role of UHRF2 in cell motility and invasion through the regulation of the epithelial- mesenchymal transition (EMT) process by acting as a transcriptional co-regulator of the EMT-transcription factors (TFs). We ectopically expressed UHRF2 in gastric cancer cell lines and performed multidimensional proteomics analyses. Proteome profiling analysis suggested a role of UHRF2 in repression of cell-cell adhesion; analysis of proteome-wide TF DNA binding activities revealed the up-regulation of many EMT-TFs in UHRF2-overexpressing cells. These data suggest that UHRF2 is a regulator of cell motility and the EMT program. Indeed, cell invasion experiments demonstrated that silencing of UHRF2 in aggressive cells impaired their abilities of migration and invasion in vitro. Further ChIP-seq identified UHRF2 genomic binding motifs that coincide with several TF binding motifs including EMT-TFs, and the binding of UHRF2 to CDH1 promoter was validated by ChIP-qPCR. Moreover, the interactome analysis with IP-MS uncovered the interaction of UHRF2 with TFs including TCF7L2 and several protein complexes that regulate chromatin remodeling and histone modifications, suggesting that UHRF2 is a transcription co-regulator for TFs such as TCF7L2 to regulate the EMT process. Taken together, our study identified a role of UHRF2 in EMT and tumor metastasis and demonstrated an effective approach to obtain clues of UHRF2 function without prior knowledge through combining evidence from multidimensional proteomics analyses. |
| URI | http://hdl.handle.net/20.500.11897/433970 |
| ISSN | 1535-9476 |
| DOI | 10.1074/mcp.M115.057448 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京肿瘤医院 |
