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Expression data from p63 siRNA in squamous cell lines

ABSTRACT: p63, a homologue of the tumor suppressor p53, is critical for the development and maintenance of squamous epithelia. p63 is specifically expressed in the basal layers of stratified epithelial tissues, and is considered to be a specific marker for cells of this type. The role of p63 in tumorigenesis remains poorly defined. Numerous studies have highlighted the oncogenic potential of the predominant p63 isoform, ΔNp63α; however, data suggests that other p63 proteins can act as tumor suppressors or alter the metastatic potential of tumors. ΔNp63α can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological role is still unclear. In this study, we used a loss-of-function approach to investigate the transcriptional programs controlled by p63. Keywords: cell line panel

ORGANISM(S): Homo sapiens

PROVIDER: GSE4975 | GEO | 2006/06/06

SECONDARY ACCESSION(S): PRJNA95479

REPOSITORIES: GEO

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siRNA profiling of human keratinocyte and squamous cell carcinoma cell lines knocked down with p63 reveals loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis

Project description:p63, a homologue of the tumor suppressor p53, is critical for the development and maintenance of squamous epithelia. p63 is specifically expressed in the basal layers of stratified epithelial tissues and is considered a specific marker for cells of this type. The role of p63 in tumorigenesis remains poorly defined. Numerous studies have highlighted the oncogenic potential of the predominant p63 isoform DeltaNp63alpha; however, data suggest that other p63 proteins can act as tumor suppressors or alter the metastatic potential of tumors. DeltaNp63alpha can act as a transcriptional repressor, but the link between the transcriptional functions of p63 and its biological role is still unclear. In this study, we used a loss-of-function approach to investigate the transcriptional programs controlled by p63. Disruption of p63 in squamous cell lines resulted in down-regulation of transcripts specifically expressed in squamous tissues and a significant alteration of keratinocyte differentiation. Interestingly, we found that disruption of p63 led to up-regulation of markers of nonepithelial tissues (mesenchyme and neural tissue) in both primary and immortalized squamous cells. Many of these up-regulated genes are associated with increased capacity for invasion and metastasis in tumors. Furthermore, loss of p63 expression was accompanied by a shift toward mesenchymal morphology and an increase in motility in primary keratinocytes and squamous cell lines. We conclude that loss of endogenous p63 expression results in up-regulation of genes associated with invasion and metastasis, and predisposes to a loss of epithelial and acquisition of mesenchymal characteristics. These findings have implications for the role of p63 in both development and tumorigenesis.

2007-11-11 | E-GEOD-4975 | biostudies-arrayexpress

Mutant p63 disrupts the key specification switch from the multipotent cell state to stratified epithelia during epithelial differentiation/in ectodermal dysplasia disorders

Project description:Transcription factor p63 is a key regulator of stratified epithelia. In humans mutations in p63 are associated with developmental disorders that manifest defects in stratified epithelia including the epidermis. We established an epidermal commitment model using human pluripotent stem cells (PSCs) and characterized differentiation defects of PSCs carrying p63 mutations. Transcriptome analyses revealed distinct phases of epidermal commitment, multipotent simple epithelial, basal stratified epithelial and mature epidermal fates. Differentiation defects of p63 mutant PSCs occurred during the specification switch from the simple epithelium to the basal stratified epithelial fate. Single-cell transcriptome and pseudotime analyses identified enhanced mesodermal signatures associated with the deviated commitment route of p63 mutant PSCs. Repressing mesodermal differentiation improved epidermal commitment of PSCs. Our study demonstrate that p63 is required for specification of stratified epithelia but not sufficient for epidermal maturation. It provides insights into disease mechanisms underlying defects of stratified epithelia caused by p63 mutations.

2019-08-19 | GSE120107 | GEO

Gene expression profiles induced by knockdown and overexpression of p63 variants in MCF-10A mammary epithelial cell line

Project description:p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. The p63 transactivating (TA) isoforms contain an amino-terminal exon that encodes a p53-like transactivation domain, whereas ΔN-isoforms lack this domain but contain the common DNA binding domain (DBD), suggesting that TAp63 and ΔNp63 isoforms may have opposing functions. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63γ or ΔNp63α isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis.

2010-03-12 | GSE20286 | GEO

Whole genome mapping of p63 binding sites in ME180 human cervical carcinoma cells

Project description:Using tiled microarrays covering the entire human genome, we identify ~5800 target sites for p63, a homolog of the p53 tumor suppressor essential for stratified epithelial development and implicated in epithelial stem cell maintenance. Keywords: ChIP-chip

2006-12-01 | GSE6132 | GEO

p63 spatio-temporal control of cleft palate

Project description:Cleft palate is a common congenital anomaly with a live birth prevalence estimated to be 1:2500 live births, that results from failure of growth, elevation, adhesion and/or fusion of the palatal shelves during embryogenesis. Mutations in the gene encoding the transcription factor p63 result in cleft palate in humans and mice. To study the roles of P63 in periderm migration and medial edge epithelia in mice sub-mucous cleft palate, ÎNp63alpha was ectopically expressed in the palatal epithelia using a transgenic approach.

2017-06-12 | E-MTAB-5289 | biostudies-arrayexpress

Colon cancer stem cell over-expressing ΔNp63α

Project description:p63, a member of p53 family, is transcribed in different variants, containing (TA) or lacking (ΔN) the N-terminal transactivation domain. Although the proteins of p53 family share high sequence and structural similarities, distinct functions for p63 are emerging. Here we provided a quantitative proteomic analysis by stable isotope dimethyl labeling of colon cancer stem cells over-expressing ΔNp63α in order to investigate the cellular pathways modulated by this p63 isoform.

2014-03-17 | PXD000769 | Pride

miRNA array after p63 knock down in human squamous cell carcinoma

Project description:A central challenge in human cancer therapy is the identification of pathways that control tumor cell survival and chemosensitivity in the absence of functional p53. The p53-related transcription factors p63 and p73 exhibit distinct, p53-independent roles in development and cancer: p73 promotes genome stability and mediates chemosensitivity, while p63 largely lacks these p53-like functions and instead promotes proliferation and cell survival. Here, we identify a new and physiologically important mechanism of p63/p73 cross-talk which governs the balance between pro-survival and pro-apoptotic programs in both human and murine squamous cell carcinoma. Through comprehensive profiling of p63-regulated microRNAs (miRs), we identified a subset which target p73 for inhibition, including miR-193a-5p, a direct endogenous transcriptional target repressed by p63 and activated by pro-apoptotic p73 isoforms in both normal cells and tumor cells in vivo. Consequently, chemotherapy treatment causes p63/p73-dependent induction of this miR, thereby limiting chemosensitivity due to miR-mediated feedback control of p73. We demonstrate that interrupting this feedback by inhibiting miR-193a suppresses tumor cell viability and induces dramatic chemosensitivity both in vitro and in vivo. Thus, we have identified a direct, miR-dependent regulatory circuit mediating inducible chemoresistance, whose inhibition provides a new therapeutic opportunity in p53-deficient tumors. Knockdown of endogenous p63 by p63-directed or control lentiviral shRNA in JHU-029 human SCC cells at 48h, in duplicate experiments. Array analysis showing the fold-change and direction of change for all miRs regulated > 1.5-fold in p63-ablated versus control samples

2010-11-23 | E-GEOD-25524 | biostudies-arrayexpress

ChIP-Seq Samples for p63 in HNSCC Cells to Investigate How ACTL6A and p63 Activate Hippo-YAP in SCC

Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.

2016-11-18 | GSE88859 | GEO

microRNA expression profile of MCF7 cells with retroviral inducible expression of ΔNp63α [miRNA]

Project description:MCF7 is a breast adenocarcinoma cell line which exhibits properties of differentiated luminal epithelial cells. ΔNp63α, an N-terminally truncated isoform of p51/p63 protein, plays a critical role in mammary gland development. Here, we inducibly express ΔNp63α in MCF7 cells and studied its role in stemness of breast cancer cells.

2015-12-28 | GSE64954 | GEO

mRNA expression profile of MCF7 cells with retroviral inducible expression of ΔNp63α [total RNA]

2015-12-28 | GSE64953 | GEO

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