DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail

Rei Mimoto; Naoe Taira; Hiroyuki Takahashi; Tomoko Yamaguchi; Masataka Okabe; Ken Uchida; Yoshio Miki; Kiyotsugu Yoshida

doi:10.1016/j.canlet.2013.06.005

DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail

Cancer Lett. 2013 Oct 10;339(2):214-25. doi: 10.1016/j.canlet.2013.06.005. Epub 2013 Jun 18.

Authors

Rei Mimoto¹, Naoe Taira, Hiroyuki Takahashi, Tomoko Yamaguchi, Masataka Okabe, Ken Uchida, Yoshio Miki, Kiyotsugu Yoshida

Affiliation

¹ Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan; Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan; Department of Anatomy, The Jikei University School of Medicine, Tokyo, Japan.

PMID: 23791882
DOI: 10.1016/j.canlet.2013.06.005

Abstract

The epithelial-mesenchymal transition (EMT) plays a fundamental role in the early stages of breast cancer invasion. Snail, a zinc finger transcriptional repressor, is an important regulator of EMT. Snail is phosphorylated by GSK3β and is subsequently degraded by βTrCP-mediated ubiquitination. We identified an additional kinase, DYRK2, that regulates Snail stability. Knockdown of DYRK2 promoted EMT and cancer invasion in vitro and in vivo. Consistent with these results, DYRK2 was found to be down-regulated in human breast cancer tissue. Patients with low DYRK2-expressing tumors had a worse outcome than those with high DYRK2-expressing tumors. These findings revealed that DYRK2 regulates cancer invasion and metastasis by degrading Snail.

Keywords: Breast cancer; DYRK2; E-cadherin; EMT; Snail.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / mortality
Breast Neoplasms / pathology
Cadherins / metabolism
Cell Line, Tumor
Dyrk Kinases
Epithelial-Mesenchymal Transition* / genetics
Female
Gene Expression
Gene Silencing
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Phosphorylation
Prognosis
Proteasome Endopeptidase Complex / metabolism
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Protein Stability
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / metabolism*
Proteolysis
Signal Transduction
Snail Family Transcription Factors
Transcription Factors / metabolism*
Ubiquitin / metabolism

Substances

Cadherins
Snail Family Transcription Factors
Transcription Factors
Ubiquitin
Protein-Tyrosine Kinases
Protein Serine-Threonine Kinases
Proteasome Endopeptidase Complex