title: p63 attenuates epithelial to mesenchymal potential in an experimental prostate cell model.
abstract: The transcription factor p63 is central for epithelial homeostasis and development. In our model of epithelial to mesenchymal transition (EMT) in human prostate cells, p63 was one of the most down-regulated transcription factors during EMT. We therefore investigated the role of p63 in EMT. Over-expression of the predominant epithelial isoform ΔNp63α in mesenchymal type cells of the model led to gain of several epithelial characteristics without resulting in a complete mesenchymal to epithelial transition (MET). This was corroborated by a reciprocal effect when p63 was knocked down in epithelial EP156T cells. Global gene expression analyses showed that ΔNp63α induced gene modules involved in both cell-to-cell and cell-to-extracellular-matrix junctions in mesenchymal type cells. Genome-wide analysis of p63 binding sites using ChIP-seq analyses confirmed binding of p63 to regulatory areas of genes associated with cell adhesion in prostate epithelial cells. DH1 and ZEB1 are two elemental factors in the control of EMT. Over-expression and knock-down of these factors, respectively, were not sufficient alone or in combination with ΔNp63α to reverse completely the mesenchymal phenotype. The partial reversion of epithelial to mesenchymal transition might reflect the ability of ΔNp63α, as a key co-ordinator of several epithelial gene expression modules, to reduce epithelial to mesenchymal plasticity (EMP). The utility of ΔNp63α expression and the potential of reduced EMP in order to counteract metastasis warrant further investigation.
authors: The Gade Institute, University of Bergen, Bergen, Norway.
authors: Jan Roger
authors: JR
authors: Olsen
authors: Anne Margrete
authors: AM
authors: Oyan
authors: Kari
authors: K
authors: Rostad
authors: Margrete R
authors: MR
authors: Hellem
authors: Jie
authors: J
authors: Liu
authors: Lisha
authors: L
authors: Li
authors: David R
authors: DR
authors: Micklem
authors: Hallvard
authors: H
authors: Haugen
authors: James B
authors: JB
authors: Lorens
authors: Varda
authors: V
authors: Rotter
authors: Xi-Song
authors: XS
authors: Ke
authors: Biaoyang
authors: B
authors: Lin
authors: Karl-Henning
authors: KH
authors: Kalland
mesh_terms: D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape; D016384:Consensus Sequence; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D063990:Gene Ontology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D007797:Laminin / Q000235:genetics; D008297:Male; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; C400567:LAMC2 protein, human; D007797:Laminin; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
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