title: The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression.
abstract: Plakophilin 3 (PKP3) belongs to the p120ctn family of armadillo-related proteins predominantly functioning in desmosome formation. Here we report that PKP3 is transcriptionally repressed by the E-cadherin repressor ZEB1 in metastatic cancer cells. ZEB1 physically associates with two conserved E-box elements in the PKP3 promoter and partially represses the activity of corresponding human and mouse PKP3 promoter fragments in reporter gene assays. In human tumours ZEB1 is upregulated in invasive cancer cells at the tumour-host interface, which is accompanied by downregulation of PKP3 expression levels. Hence, the transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition.
authors: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
authors: Kirsten
authors: K
authors: Aigner
authors: Luise
authors: L
authors: Descovich
authors: Mario
authors: M
authors: Mikula
authors: Aneesa
authors: A
authors: Sultan
authors: Brigitta
authors: B
authors: Dampier
authors: Stefan
authors: S
authors: Bonné
authors: Frans
authors: F
authors: van Roy
authors: Wolfgang
authors: W
authors: Mikulits
authors: Martin
authors: M
authors: Schreiber
authors: Thomas
authors: T
authors: Brabletz
authors: Wolfgang
authors: W
authors: Sommergruber
authors: Norbert
authors: N
authors: Schweifer
authors: Andreas
authors: A
authors: Wernitznig
authors: Hartmut
authors: H
authors: Beug
authors: Roland
authors: R
authors: Foisner
authors: Andreas
authors: A
authors: Eger
mesh_terms: D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D051191:Plakophilins / Q000032:analysis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C495339:PKP3 protein, human; D051191:Plakophilins; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1