Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-sequencing of mouse mammary tumor organoids that were modified to generate knockout lines for SOX4

ABSTRACT: The transcription factor SOX4 is widely expressed during development and is essential to maintain progenitor pools in a variety of organs. In breast cancer SOX4 has been shown to be associated with poor survival and increased tumor size and metastasis formation. This has mostly been attributed to the ability of SOX4 to regulate Epithelial-to-Mesenchymal-Transition (EMT). However, SOX4 regulates target gene transcription in a plastic manner that is dependent on the cellular and epigenetic context. In this study we have investigated the loss of SOX4 in mammary tumor development utilizing organoids derived from a PyMT genetic mouse model. CRISPR-mediated loss of SOX4 led to a strong impairment in growth of primary mammary tumors and subsequent metastases through an EMT-independent mechanism. Instead, SOX4 is required for inhibiting differentiation by controlling genes that are highly activated in foetal mammary stem cells (fMaSC). These SOX4-dependent genes are associated with cell cycle progression, DNA biosynthesis, RNA processing and ribosome biogenesis suggesting that SOX4 controls active cycling of tumor cells. Analysis of genes co-expressed with SOX4 in the TCGA and METABRIC studies revealed that these cell cycle-related genes correlate with SOX4 expression in human tumors. Our study identifies a novel role for SOX4 in maintaining mammary tumors in an undifferentiated proliferative state.

ORGANISM(S): Mus musculus

PROVIDER: GSE153190 | GEO | 2021/09/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Sox4 is a master regulator of epithelial-mesenchymal transition (EMT) by controlling Ezh2 expression and epigenetic reprogramming

Project description:Gene expression profiling has uncovered the transcription factor Sox4 with up-regulated activity during TGFÎ²-induced EMT in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, while forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2. Our Dataset comprises of 12 ChIP-seq samples using chromatin from NMuMG cells which was immunoprecipitated using H3K27me3-specific antibody during TGFÎ²-induced EMT (2ng/ml) at 6 different stages (day 0, 1, 4, 7, 10, 20).

2013-06-20 | E-GEOD-45579 | biostudies-arrayexpress

Sox4 is a master regulator of epithelial-mesenchymal transition (EMT) by controlling Ezh2 expression and epigenetic reprogramming

Project description:Gene expression profiling has uncovered the transcription factor Sox4 with up-regulated activity during TGFβ-induced EMT in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, while forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.

2013-06-20 | GSE45579 | GEO

Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis

Project description:The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the tumor-type. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and thereby promotes tumor-induced angiogenesis both in vitro and in vivo. Furthermore, in breast tumors, SOX4 expression correlates with blood vessel density and size, and predicts poor-prognosis in breast cancer patients. Our data provide novel mechanistic insights into context-dependent SOX4 target gene selection, and uncover a novel pro-oncogenic role by promoting tumor-induced angiogenesis. These findings establish a key role for SOX4 in promoting metastasis through exploiting diverse pro-tumorigenic pathways.

2020-01-01 | GSE99256 | GEO

Sox4 links tumor suppression to accelerated aging in mice [Telogen]

Project description:Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer. Sox4 WT and cKO (conditional KO in skin) skin was collected for microarray hybridization, to study the contribution of Sox4 to skin homeostasis in basal conditions (Telogen)

2015-05-20 | E-GEOD-58154 | biostudies-arrayexpress

Sox4 links tumor suppression to accelerated aging in mice [Hair regeneration]

Project description:Sox4 is a transcription factor expressed during embryonic development and some adult tissues such as lymphoid organs, pancreas, intestine and skin. During embryogenesis, Sox4 regulates the survival of mesenchymal and neural progenitors, lymphocyte and myeloid differentiation, and pancreatic, bone and cardiac development. Aberrantly increased Sox4 expression is linked to malignant transformation and metastasis in several types of human cancer. To study the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display a plethora of age-related degenerative disorders and reduced spontaneous cancer incidence, indicating a role for this protein in maintaining adult tissue homeostasis and in tumor growth. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and DNA damage accumulation, accompanied by resistance to chemical carcinogenesis. These phenotypes correlate with downregulation of cell cycle, DNA repair and skin stem cell genes in the absence of Sox4. Altogether, these findings highlight the importance of Sox4 in adult tissue homeostasis and cancer. Sox4 WT and cKO (conditional KO in skin) were plucked and skin was collected for microarray hibridization, to study the contribution of Sox4 to hair regeneration and hair follicle stem cell activation

2015-05-20 | E-GEOD-58153 | biostudies-arrayexpress

Genes regulated by SOX4 in glioblastoma cell line

Project description:Overexpression of SOX4 in LN229 glioblastoma cells prevents their cell cycle We used microarrays to detail the global programme of gene expression in SOX4 overexpression LN229 cells compared with mock control LN229 cells SOX4 overexpression LN229 cells and and control LN229 cells were cultured in DMEM cell culture media for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the genes regulated by SOX4 in glioblastoma cell lines.

2014-09-30 | E-GEOD-51301 | biostudies-arrayexpress

Sox4 knockdown in ACC3 cells

Project description:Sox4 is upregulated in adenoid cystic carcinoma (ACC). The ACC3 cell line is the most widely available cell culture model system of this tumor type. RNAi mediated knockdown of Sox4 in ACC3 cells induces apoptosis. Since Sox4 is a transcription factor, it is hypothesized that this apoptotic phenotype is due to changes in transcription from genes under Sox4 control.This experiment was designed to find candidate genes whose expression levels change after Sox4 knockdown that could contribute to the pro-apoptotic phenotype. Keywords: gene knockdown

2006-07-28 | GSE4225 | GEO

SOX4 genome binding targets in glioblastoma cell line

Project description:Overexpression of SOX4 in LN229 glioblastoma cells prevents their cell cycle Examination of SOX4 binding profile in prostate cell LN229-SOX4 with LN229-GFP as negative control.

2014-10-20 | E-GEOD-51663 | biostudies-arrayexpress

Sox4 links tumor suppression to accelerated aging in mice [Telogen]

2015-05-20 | GSE58154 | GEO

Expression data from Sox4 knockdown cells in the presence and absence of TGFÎ² in NMuMG cells

Project description:Expression profiling after Sox4 knockdown (KD) during epithelial to mesenchymal transition (EMT) in NMuMG reveals a significant number of genes that are transcriptionally deregulated. Gene expression profiling is performed in Sox4-ablated (siSox4) NMuMG cells. Cells transfected with siControl is used as a control. The cells were either treated with transforming growth factor-beta (TGFÎ²; 2ng/ml) or not.

2013-06-20 | E-GEOD-44050 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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