The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression.
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.
Aigner
Kirsten
K
Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
Descovich
Luise
L
Mikula
Mario
M
Sultan
Aneesa
A
Dampier
Brigitta
B
Bonné
Stefan
S
van Roy
Frans
F
Mikulits
Wolfgang
W
Schreiber
Martin
M
Brabletz
Thomas
T
Sommergruber
Wolfgang
W
Schweifer
Norbert
N
Wernitznig
Andreas
A
Beug
Hartmut
H
Foisner
Roland
R
Eger
Andreas
A
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
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