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

Oncogene (2014-03-26)
W-L Wang, H-C Huang, S-H Kao, Y-C Hsu, Y-T Wang, K-C Li, Y-J Chen, S-L Yu, S-P Wang, T-H Hsiao, P-C Yang, T-M Hong
ABSTRACT

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.

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