Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [CUTnTag_Ezh2i]

ABSTRACT: While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242436 | GEO | 2024/07/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [RNAseq_ip63]

Project description:While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

2024-07-26 | GSE242463 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [RNAseq_Ezh2i]

2024-07-26 | GSE242439 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [CUTnTag_ip63]

2024-07-26 | GSE242437 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [RNAseq_Eso]

2024-07-26 | GSE242438 | GEO

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [ChIP-seq]

2024-07-26 | GSE264639 | GEO

Single cell RNA-sequencing of esophageal epithelium from wild type and p63-KO mice

Project description:Cell fate determination and maintenance play critical roles in establishing and preserving tissue identity and function during organ development. Aberrant cell fate transitions can lead to cancer cells acquiring lineage plasticity, resulting in tumor heterogeneity and resistance to treatment. Trp63 (p63) is a transcription factor important for the formation of stratified squamous epithelium in the esophagus. Here, we report an unexpected role of p63 in protecting esophageal basal progenitor cells from committing to a neuroendocrine fate. Combination of single cell RNA sequencing analysis, lineage tracing and in vitro differentiation, we found that deletion of p63 in developing murine esophagus and in human embryonic stem cells results in extensive differentiation towards neuroendocrine lineage.

2024-07-25 | GSE263694 | GEO

Expression data from p63 siRNA in squamous cell lines

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 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

2006-06-06 | GSE4975 | GEO

Hypoxa-actived XBP1s recruits HDAC2-EZH2 to engage epigenetic suppression of DNp63 expression and promotes breast cacner metastasis independent HIF1a

Project description:Hypoxia is a hallmark of cancer development. However, the molecular mechanisms by which hypoxia promotes tumor metastasis are not fully understood. In this study, we demonstrate that hypoxia promotes breast cancer metastasis through suppression of ΔNp63α-dependent in a HIF1α-independent manner. We show that hypoxia activates unfolded protein response (UPR) to elevate XBP1s, which in turn forms stable repressor protein complexes with HDAC2 and EZH2 in suppression of ΔNp63α. Notably, while H3K27ac is predominantly presented in the ΔNp63 promoter under normoxia, it is switched to H3K27me3 under hypoxia. We show that XBP1s binds to the ΔNp63 promoter to recruit HDAC2 and EZH2 in facilitating the H3K27ac-H3K27me3 switch. Knockdown or pharmacological inhibition of either HDAC2 or EZH2 leads to increased H3K27ac concomitant with reduced H3K27me3, which effectively restores ΔNp63α expression suppressed by hypoxia, resulting in inhibition of cell migration. Clinical analyses reveal that reduced p63 expression is correlated with the elevated expression of XBP1, HDAC2, or EZH2, and is associated with poor overall survival in human breast cancer patients. Together, these results indicate that hypoxia-activated XBP1s modulates the epigenetic program in suppression of ΔNp63α to promote breast cancer metastasis independent of HIF1α and provides a molecule basis for targeting the XBP1s/HDAC2/EZH2-ΔNp63α axis as a putative strategy in the treatment of breast cancer metastasis.

2024-01-24 | GSE253833 | GEO

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

SOX2 and p63 occupancy in human squamous carcinoma cell lines and embryonic stem cells.

Project description:SOX2 is a transcription factor essential for pluripotent stem cells, and development and maintenance of squamous epithelium. We previously reported SOX2 an oncogene subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here we demonstrate in SCCs that SOX2 interacts with another master squamous transcription factor p63, and through ChIP-seq show that genomic occupancy of SOX2 overlaps with that of p63 at a large number of loci and that they cooperatively regulate gene expression including ETV4, which we find essential for SOX2-amplified SCC cell survival. Furthermore, SOX2 binds to distinct genomic loci in SCCs than in embryonic stem cells and the SOX2-p63 coordinate binding is unique to SCC. In addition, a subset of SOX2 genomic binding sites in SCC that lack p63 co-occupancy are co-occupied by the AP-1 transcriptional complex. These demonstrate that SOX2’s actions in SCC differ substantially from its role in pluripotency and identify novel SOX2 interactions that will enable deeper characterization of SOX2’s function in SCC. SOX2 and p63 ChIP-seq from three lung and esophageal squamous carcinoma cell lines with amplification of SOX2 as well as SOX2 ChIP-seq from an ES cells.

2014-03-12 | E-GEOD-46837 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data