title: DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail.
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.
authors.affiliation: 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.
authors.forename: Rei
authors.initials: R
authors.lastname: Mimoto
authors.forename: Naoe
authors.initials: N
authors.lastname: Taira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Masataka
authors.initials: M
authors.lastname: Okabe
authors.forename: Ken
authors.initials: K
authors.lastname: Uchida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.forename: Kiyotsugu
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D000097603:Dyrk Kinases
chemical_list: D015820:Cadherins; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D025801:Ubiquitin; D000097603:Dyrk Kinases
keywords: Breast cancer; DYRK2; E-cadherin; EMT; Snail