Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Basonuclin-2 regulates extracellular matrix production and degradation

ABSTRACT: Epithelial-Mesenchymal Transition (EMT) is essential for tissue patterning and organization. It involves both regulation of cell motility and alterations in the composition and organization of the extracellular matrix (ECM); a complex environment of proteoglycans and fibrous proteins that promotes tissue homeostasis, regulates signaling in response to chemical and biomechanical stimuli and is often dysregulated in diseases such as cancer and fibrosis. Here, we demonstrate that Basonuclin-2 (BNC2), a mesenchymal-expressed gene that has been widely associated with cancer and developmental defects by genome-wide association study (GWAS), is a novel regulator of ECM composition and degradation. We find that at endogenous levels, BNC2 controls the expression of specific collagens, matrix metalloproteases and other matrisomal components in breast cancer cells, and in fibroblasts that are primarily responsible for the deposition and processing of the ECM within the tumour microenvironment. In so doing, BNC2 modulates the motile and invasive properties of cancers which likely explains the association of high BNC2 expression with increasing cancer grade and poor patient prognosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221228 | GEO | 2023/08/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Basonuclin: A novel mammalian maternal effect gene

Project description:Basonuclin, which is a zinc-finger protein found in abundance only in the keratinocytes of the stratified epithelium, male germ cells and oocytes, qualifies as a maternal-effect gene because the source of pre-implantation embryonic basonuclin is maternal. Using a transgenic-RNAi approach, we knocked-down basonuclin specifically in mouse oocytes, which led to female sub-fertility. Basonuclin deficiency in oocytes perturbed both RNA polymerase I- and II-mediated transcription and oocyte morphology was affected as evidenced by cytoplasmic and cell surface abnormalities. The affected oocytes, however, could still mature to and arrest at metaphase II and be ovulated, suggesting the impaired pathways were not essential for oocyte development and maturation. Nevertheless, an early embryonic failure in pre-implantation development was identified and likely accounted for the sub-fertility phenotype. These results suggest that basonuclin is a new member of the mammalian maternal-effect genes and interestingly, differs from the previously reported mammalian maternal-effect genes in that it also apparently perturbs oogenesis. Keywords: RNAi knockdown

2006-05-01 | GSE4029 | GEO

RNAi knock down of basonuclin in mouse oodcytes reveals basonuclin is a new member of the mammalian maternal-effect genes

2007-07-06 | E-GEOD-4029 | biostudies-arrayexpress

Analysis of extracellular matrix proteins from 3D cultures of primary prostate fibroblasts, DU145 cells and mixed cells

Project description:Composition and organization of extracellular matrix (ECM) in tumor stroma are important regulators of cancer cell behavior. Therefore, ECM produced by cancer associated fibroblasts is often used in in vitro experiments. Here, a proteome wide analysis of ECM proteins in 3D culture is analysed.

2018-03-13 | PXD006563 | Pride

Basonuclin-1 modulates epithelial plasticity and TGF-?1-induced loss of epithelial cell integrity [BNC1]

Project description:TGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). Several transcription factors, some of them being TGF-b1-responsive, are functionally involved in such a switch and affect epithelial differentiation and plasticity. We used microarray-based gene expression profiling of mammary epithelial cells that actively undergo TGF-b1-induced epithelial dedifferentiation. Further, we determined gene expression changes in Basonuclin-1 knock-down cells in conjunction with TGF-b1-stimulation in order to determine a possible effect of Bnc1 on TGF-b1-responsive genes. Cells were transfected with non-silencing (control) siRNA or siRNA against Basonuclin-1 (Bnc1) for 24hrs. Subsequently, cells were treated with 5ng/ml TGF-b1 or left untreated for additional 24hrs. The experiments were performed as independent biological triplicate.

2014-03-01 | E-GEOD-54715 | biostudies-arrayexpress

Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer

Project description:Chronic inflammation underlies tumor initiation, progression, invasion, and metastasis. In the colon, long-term exposure to chronic inflammation drives colitis associated colon cancer (CAC) in patients with inflammatory bowel disease (IBD). While the causal and clinical links between chronic inflammation and CAC are well established, our molecular understanding of how chronic inflammation leads to the development of colon cancer is still lacking. Here we deconstruct the evolving microenvironment of CAC, by measuring proteomic changes and extracellular matrix (ECM) organization over time in a genetically modified mouse model of CAC. We detect early changes in ECM structure and composition, and report that the transcriptional regulator heat shock factor 1 (HSF1) plays a crucial role in orchestrating these events. Activated in stromal fibroblasts of the gut, HSF1 promotes ECM remodeling and inflammatory programs which lead to the development of CAC. Loss of HSF1 abrogates ECM assembly by colon fibroblasts in cell culture, prevents inflammation-induced ECM remodeling in mice and significantly inhibits progression to CAC. Establishing the relevance of our experimental findings to human disease, we find high activation of stromal HSF1 in CAC patients, and detect the HSF1-dependent proteomic ECM signature in human colorectal cancer. Thus, HSF1-dependent ECM remodeling plays a crucial role in mediating inflammation-driven colon cancer.

2020-11-05 | GSE158276 | GEO

Selvaggio2020 - Microenvironment control of hybrid Epithelial-Mesenchymal phenotypes

Project description:Epithelial to Mesenchymal Transition (EMT) has been associated with cancer cell heterogeneity, plasticity and metastasis. It has been the subject of several modeling effort. This logical model of the EMT cellular network aims to assess microenvironmental signals controlling cancer-associated phenotypes amid the EMT continuum. Its outcomes relate to the qualitative degrees of cell adhesions by adherent junctions and focal adhesions, two features affected during EMT. Model attractors recover epithelial, mesenchymal and hybrid phenotypes, and simulations show that hybrid phenotypes may arise through independent molecular paths, involving stringent extrinsic signals. Of particular interest, model predictions and their experimental validations indicated that: 1) ECM stiffening is a prerequisite for cells overactivating FAK-SRC to upregulate SNAIL1 and acquire a mesenchymal phenotype, and 2) FAK-SRC inhibition of cell-cell contacts through the Receptor Protein Tyrosine Phosphates kappa leads to the acquisition of a full mesenchymal rather than a hybrid phenotype.

2020-06-30 | MODEL2004040001 | BioModels

Transcriptomic profiling of DU4475 cells in 3D cell culture matrices and suspension

Project description:The extracellular matrix (ECM)-regulated phenotypic plasticity is crucial for metastatic progression of triple negative breast cancer (TNBC). To investigate the effect of matrix cues on phenotypic plasticity, we embedded triple negative DU4475 cells from suspension culture into mechanically tunable fibrin gels or basement membrane extract (Matrigel). Cells in suspension culture and matrix cultures showed divergent gene expression profiles, with specific gene expression signatures depending on the biochemical composition and stiffness of the matrix.

2023-04-05 | GSE228939 | GEO

Characterization of Chemotherapy-treated PyMT Liver Matrisome

Project description:Metastasis accounts for 90% of cancer-related deaths, yet the mechanisms by which cancer cells colonize secondary organs remain poorly understood. For breast cancer patients, metastasis to the liver is associated with poor prognosis and a median survival of 6 months. Standard of care is chemotherapy, but recurrence occurs in 30% of patients. Systemic chemotherapy has been shown to induce hepatotoxicity and fibrosis, but how chemotherapy impacts the composition of the liver extracellular matrix (ECM) remains unknown. Individual ECM proteins drive tumor cell proliferation and invasion, features that are essential for metastatic outgrowth in the liver. Here, we characterize the liver ECM of tumor-bearing mice treated with and without chemotherapy using the MMTV-PyMT transgenic model of breast cancer. We identify distinct drug-specific changes induced by commonly used cytotoxic chemotherapies. We identify Collagen V as an ECM protein that is more abundant in livers isolated from paclitaxel-treated mice and identify mechanisms of Collagen V driven invasion via ECM organization and signaling through α1β1 integrins.

2022-10-05 | PXD036736 | Pride

TGFb-induced transcriptome profile in cancer cell lines

Project description:TGFb plays many roles during tumor progression. It inhibits epithelial cell proliferation in the early stage but promotes tumor invasion by inducing epithelial-to-mesenchymal transition (EMT) in the late stage. Coupled with the strong EMT effect, TGFb exerts an overwhelming influence on modifying the extracellular matrix (ECM), which is generally thought to favor the adhesion and migration of tumor cells [4]. However, the regulation and function of ECM deposited in the tumor microenvironment by TGFb signaling have not been elucidated. Here, we performed a transcriptomic analysis using the human prostate cancer PC3U cell line and the human A549 lung carcinoma cell line. The top-upregulated genes in PC3U cells and A549 cells upon TGFb stimulation were identified to analyze the main regulatory function elicited by TGFb signaling. The GO enrichment analysis showed that extracellular matrix organization and the positive regulation of cell migration were the top regulatory functions.

2024-09-12 | GSE274287 | GEO

Developmental pathways pervade stem cell responses to evolving extracellular matrices of 3D bioprinted microenvironments

Project description:Developmental studies and 3D in vitro model systems show the production and engagement of extracellular matrix (ECM) often precedes stem cell differentiation. Yet unclear is how the ECM triggers signaling events in sequence to accommodate multistep processes characteristic of differentiation. Here we employ transcriptome profiling and advanced imaging to delineate the specificity of ECM engagement to particular differentiation pathways and to determine whether specificity in this context is a function of long term ECM remodeling. To this end, human mesenchymal stem cells (hMSCs) were cultured in 3D bioprinted matrices created from ECM proteins and associated controls. We found exogenous ECM provided in 3D microenvironments at early time points impacts on the composition of microenvironments at later time points and that each evolving 3D microenvironment is uniquely poised to promote stem cell differentiation. Moreover, 2D cultures undergo minimal ECM remodeling and are ill-equipped to stimulate pathways associated with development.

2018-01-01 | GSE102737 | GEO

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