Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

ABSTRACT: ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

PROVIDER: PRJNA205866 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling.

Project description:Emerging evidence suggests that cancer is populated and maintained by tumour-initiating cells (TICs) with stem-like properties similar to those of adult tissue stem cells. Despite recent advances, the molecular regulatory mechanisms that may be shared between normal and malignant stem cells remain poorly understood. Here we show that the ΔNp63 isoform of the Trp63 transcription factor promotes normal mammary stem cell (MaSC) activity by increasing the expression of the Wnt receptor Fzd7, thereby enhancing Wnt signalling. Importantly, Fzd7-dependent enhancement of Wnt signalling by ΔNp63 also governs tumour-initiating activity of the basal subtype of breast cancer. These findings establish ΔNp63 as a key regulator of stem cells in both normal and malignant mammary tissues and provide direct evidence that breast cancer TICs and normal MaSCs share common regulatory mechanisms.

| S-EPMC4183725 | biostudies-literature

ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-08-19 | E-GEOD-47493 | biostudies-arrayexpress

ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-08-19 | GSE47493 | GEO

Disrupted transcripitonal network in ΔNp63 AEC tissue model

Project description:This SuperSeries is composed of the following subset Series: GSE33495: Disrupted transcripitonal network in ΔNp63 AEC tissue model [gene expression] GSE33571: Disrupted transcriptional network in ΔNp63 AEC tissue model [ChIP-Seq] Refer to individual Series

2012-06-17 | E-GEOD-33572 | biostudies-arrayexpress

A stromal niche regulate CSCs in Wnt-Met mammary gland tumors

Project description:CSCs may be regulated by extrinsic signals provided by specialized microenvironments, or niches, which sustain CSC expansion. We investigated the role of cancer associated fibroblasts (CAFs) in the regulation of CSCs using a genetically engineered mouse model of basal-like breast cancer driven by combined activation of Wnt/β-catenin and HGF/Met signaling (Wnt-Met mice). We found that CAFs secrete soluble factors that promote the expansion of the population of self-renewing cells that generate mammospheres and enhance the capacity of CSCs to form invasive 3D structures. Using transcriptional profiling, we identified a network of paracrine interactions between CAFs and CSCs that regulate reciprocal functions.

2018-04-23 | GSE68241 | GEO

ΔNp63 controls stemness and inflammation in the adult epidermis

Project description:The p63 transcription factor is critical for epidermis formation in embryonic development, but its role in the adult epidermis is barely investigated. Here we show that acute genetic ablation of ΔNp63, the main p63 isoform, in the adult epidermis disrupts keratinocyte proliferation and self-maintenance and, unexpectedly, triggers an inflammatory psoriasis-like condition. Mechanistically, single-cell RNA sequencing revealed down-regulation of the cell cycle genes, up-regulation of differentiation markers, and induction of several pro-inflammatory pathways in ΔNp63-ablated keratinocytes. Intriguingly, ΔNp63-ablated cells disappear three weeks post-ablation, at the expense of the remaining non-ablated cells. This was not associated with active cell death mechanisms, but rather with reduced stemness and self-maintenance capacity. Indeed, in vivo wound healing assay, a physiological readout of the epidermal stem cell function, was largely impaired in the ablated skin. We found that the Wnt signaling pathway (Wnt5a, Wnt10a, Fzd6, Fzd10) and Col17a1 are the likely ΔNp63 effectors responsible for keratinocyte proliferation and stemness, while AP1 factors are responsible for excessive differentiation, and Il-1a, Il-18, Il-24 and Il-36γ for the suppression of inflammation. These data implicate ΔNp63 as a critical node that coordinates balanced epidermal homeostasis and suppression of inflammation in the adult epidermis, upstream of known regulatory pathways.

2023-03-31 | GSE213528 | GEO

Transcriptome analysis of Scramble control and Cdk14-sh mouse mammary basal cells

Project description:Wnt/β-catenin signaling pathway has become a key signaling pathway regulating mammary organogenesis and oncogenesis. However, the therapeutic methods by targeting Wnt pathway against breast cancer has been limited. To address this challenge, we investigated the function of cyclin-dependent kinase 14 (CDK14), a member of Wnt signaling pathway, in mammary development and breast cancer progression. We showed that CDK14 was expressed in the mammary basal layer and elevated in triple negative breast cancer (TNBC). CDK14 knockdown reduces colony formation ability and regeneration capacity of mammary basal cells, and significantly inhibits murine MMTV-Wnt-1 basal-like mammary tumor progression. Excitingly, knockdown of CDK14 or pharmacological inhibition of CDK14 by FMF-04-159-2 significantly inhibited the progression and metastasis of human TNBC. Mechanistically, CDK14 inhibition inhibits mammary regeneration and TNBC progression by attenuating Wnt/β-catenin signaling. Together, we demonstrated that CDK14 regulates mammary regeneration and breast tumorigenesis, and is a promising therapeutic target for TNBC.

2022-04-29 | GSE201526 | GEO

miR205 Regulates Mammary Gland Development and Stem Cell Self-renewal through YAP and Wnt signaling

Project description:Mammary gland development is fueled by stem cell self-renewal and differentiation. External cues from the microenvironment coupled with internal cues such as post-transcriptional regulation exerted by miRNAs regulate stem cell behavior and stem cell fate. We have identified a miR205 regulatory network required for mammary gland morphogenesis and stem cell maintenance. In the postnatal mammary gland, miR205 is predominantly expressed in the basal/stem cell enriched population. Conditional deletion of miR205 in mammary epithelial cells severely impaired stem cell self-renewal and mammary repopulating potential both in vitro and in vivo. miR205 null glands displayed significant changes in the basal population, basement membrane and stroma. NKD1 and PP2A-B56, which inhibit the Wnt signaling pathway, and AMOT, which causes YAP cytoplasmic retention and inactivation were identified as miR205 downstream effectors. Collectively these findings reveal an essential role of miR205 in mammary gland development.

2018-12-27 | GSE124364 | GEO

RNA-seq of mouse prostate basal cell organoids treated under different androgen and Wnt signaling conditions

Project description:To determine the role of Wnt and AR signaling pathway crosstalk on prostate basal stem cells, RNA-seq was performed for mouse prostate basal cell organoids treated under three conditions.

2023-06-28 | GSE220499 | GEO

Transcriptome analyses of luminal-derived basal cells induced by hormones in the mammary gland

Project description:We have used RNA-seq to examine RNA differential expression among three populations, normal basal cells, luminal-derived basal cells (LdBCs) and normal luminal cells.

2019-12-31 | GSE109543 | GEO

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