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

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

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1116-1125
Number of pages10
JournalOncogene
Volume34
Issue number9
DOIs
Publication statusPublished - 2015 Feb 26

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    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. (2015). Slug is temporally regulated by cyclin e in cell cycle and controls genome stability. Oncogene, 34(9), 1116-1125. https://doi.org/10.1038/onc.2014.58