Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vav proteins orchestrate a keratinocyte auto/paracrine program critical for skin tumorigenesis.

ABSTRACT: Cutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles’ heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment. The dorsal skin of WT and DKO mice (Vav2-/-;Vav3-/-) were treated with either one or four applications of phorbol ester 12-O-tetradecanoylphorbol-13 acetate (TPA) (6.8 nmol in 200 μl acetone) two days after shaving. As control, we applied 200 μl of acetone. Animals were euthanized 24 hours after treatment.

ORGANISM(S): Mus musculus

SUBMITTER: Ramón García-Escudero

PROVIDER: E-GEOD-40849 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Genomic landscape of carcinogen induced mouse skin squamous cell carcinoma: whole-genome sequencing

Project description:Low coverage whole-genome sequencing of induced murine squamous cell carcinoma. 17 samples are included.

2015-04-10 | E-MTAB-2888 | biostudies-arrayexpress

Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas)

Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. Gene expression analysis was performed on mRNA extracted from 68 papillomas: two papillomas from each of 31 FVBBX mice and a single papilloma from six additional FVBBX mice. Papillomas were harvested when mice were sacrificed due to presence of a carcinoma or termination of the experiment.

2010-12-22 | E-GEOD-21263 | biostudies-arrayexpress

Transcription profiling by array of mouse back skin of wild type and Range knockout animals after aceton treatment.

Project description:In order to identify critical changes in the genetic network of Rage signaling induced by TPA throughout a 48 h kinetic, global gene expression analysis was performed. Total RNA from untreated, 24h acetone- and 6, 12, 24, 48 h TPA-treated wt and Rage KO back skin was prepared (n=3 independent animal experiments) and hybridized on 4x44K whole mouse genome oligonucleotide microarrays.

2010-11-29 | E-MTAB-205 | biostudies-arrayexpress

Genomic landscape of carcinogen induced mouse skin squamous cell carcinoma: whole-exome sequencing

Project description:Whole-exome sequencing of induced murine squamous cell carcinoma. 26 samples are included.

2014-09-11 | E-MTAB-2887 | biostudies-arrayexpress

Inflammation and tumor susceptibility in skin cancer

Project description:This SuperSeries is composed of the following subset Series: GSE12248: Genetic architecture of murine skin inflammation and tumor susceptibility GSE21247: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (carcinomas) GSE21263: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas) GSE26273: Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (aCGH) Refer to individual Series

2010-12-22 | E-GEOD-21264 | biostudies-arrayexpress

Inflammation-Driven Carcinogenesis is Mediated through STING [skin]

Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease Total RNA obtained from DMBA or acetone treated wild type (WT) or STING deficient (SKO) mouse skin or skin tumor was examined for gene expression.

2014-05-31 | E-GEOD-57604 | biostudies-arrayexpress

Transcriptome and microRNA array analyses reveal a stimulatory effect of the phytochemical shikonin on epithelial–mesenchymal transition (EMT) in mouse skin

Project description:This SuperSeries is composed of the following subset Series: GSE32694: Transcriptome and microRNA array analyses reveal a stimulatory effect of the phytochemical shikonin on epithelial–mesenchymal transition (EMT) in mouse skin [gene expression profile] GSE32695: Transcriptome and microRNA array analyses reveal a stimulatory effect of the phytochemical shikonin on epithelial–mesenchymal transition (EMT) in mouse skin [microRNA expression profile] Refer to individual Series

2011-12-31 | E-GEOD-32696 | biostudies-arrayexpress

Inflammation-Driven Carcinogenesis is Mediated through STING

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

2014-05-31 | E-GEOD-57605 | biostudies-arrayexpress

Gene expression architecture of mouse dorsal and tail skin reveals functional differences in inflammation and cancer: TPA time course

Project description:Gene expression levels in normal tissues can differ substantially between individuals, due to inherited polymorphisms acting in cis or trans. Analysis of this variation across a population of genetically distinct individuals allows us to visualize a network of co-expressed genes under normal homeostatic conditions, and the consequences of perturbation by tissue damage or disease development. Here, we explore gene expression networks in normal adult skin from 470 genetically unique mice, and demonstrate the dependence of the architecture of signaling pathways on skin tissue location (dorsal or tail skin) and perturbation by induction of inflammation or tumorigenesis. Gene networks related to specific cell types, as well as signaling pathways including Sonic Hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is extensively rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules. Time course analysis of replicate exposure to epidermal application of TPA

2016-06-01 | E-GEOD-82067 | biostudies-arrayexpress

Transcriptome and microRNA array analyses reveal a stimulatory effect of the phytochemical shikonin on epithelial–mesenchymal transition (EMT) in mouse skin [microRNA expression profile]

Project description:We investigate and define here the in vivo biological effects of shikonin, at the transcriptome and microRNA levels, in mouse skin tissues. Through cross-examination between total RNA transcripts and microRNA data sets, we predicted that shikonin treatment may affect the epithelial–mesenchymal transition (EMT) process and the expression of related microRNAs, including 200a, 200b, 200c, 141, 205 and 429 microRNAs, in test skin tissue. Indeed, further in vivo tests on mouse abdominal skin tissue confirmed the stimulatory effect of shikonin on regulatory molecules of the EMT process in epidermal tissue. In addition, RT-PCR analyses confirmed the downregulating effects of shikonin on the expression of microRNA 205 and members of the microRNA 200 family, which are known to be involved in the EMT process. Gene expression of two RNA targets of the microRNA 200 family in EMT regulation, namely Sip1 (Zeb2) and Tcf8 (Zeb1), were consistently upregulated by shikonin treatment. We demonstrate here that shikonin can confer a potent stimulatory effect on the EMT process and suppress the associated-microRNAs expression in vivo in skin tissues. In order to systematically evaluate the effects of shikonin on mouse skin tissues, we next compared the gene expression profiles in shikonin-treated and acetone-treated skin tissues at different time points. Total RNA samples were collected at indicated time points for transcriptome and microRNA array analyses.

2011-12-31 | E-GEOD-32695 | 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