Slug is temporally regulated by cyclin E in cell cycle and controls genome stability

The transcriptional repressor Slug is best known to control epithelial–mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E–cyclin-dependent kinase 2 mediates t...

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Veröffentlicht in:Oncogene 2015-02, Vol.34 (9), p.1116-1125
Hauptverfasser: Wang, W-L, Huang, H-C, Kao, S-H, Hsu, Y-C, Wang, Y-T, Li, K-C, Chen, Y-J, Yu, S-L, Wang, S-P, Hsiao, T-H, Yang, P-C, Hong, T-M
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Sprache:eng
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Zusammenfassung:The transcriptional repressor Slug is best known to control epithelial–mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E–cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2014.58