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GSE137176
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epidermal stem cells ensure proper faring of skin homeostatic processes under both physiological and challenging conditions. Currently, the molecular events underpinning ageing within the epidermal stem cell niche are poorly understood.
Publication Title
In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We have used microarray technology to identify the transcriptional targets of Rho subfamily GTPases. This analysis indicated that murine fibroblasts transformed by these proteins show similar transcriptomal profiles. Functional annotation of the regulated genes indicate that Rho subfamily GTPases target a wide spectrum of biological functions, although loci encoding proteins linked to proliferation and DNA synthesis/transcription are up-regulated preferentially. Rho proteins promote four main networks of interacting proteins nucleated around E2F, c-Jun, c-Myc, and p53. Of those, E2F, c-Jun and c-Myc are essential for the maintenance of cell transformation. Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene expression without affecting the E2F and c-Jun pathways. Loss-of-function studies demonstrate that c-Myc is important for the blockage of cell-contact inhibition rather than for promoting the proliferation of Rho-transformed cells. However, c-Myc overexpression does not bypass the inhibition of cell transformation induced by Rock blockage, indicating that c-Myc is essential, but not sufficient, for Rock-dependent transformation. These results reveal the complexity of the genetic program orchestrated by the Rho subfamily and pinpoint protein networks that mediate different aspects of the malignant phenotype of Rho-transformed cells
Publication Title
Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played non redundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factorb family ligand inhibin bA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.
Publication Title
The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to investigate gene expression changes induced by the inhibition of RRAS2 expression using shRNA techniques to stably knockdown the endogenous transcripts of this GTPase in human MDA-MB-231-Luc cells.
Publication Title
Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
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.
Publication Title
The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Robles-Valero et al. report a tumor suppression role for the otherwise oncogenic Vav1 Rho GEF. This paradoxical action is mediated by the catalysis-independent buffering of Notch1 signaling in immature T cells.
Publication Title
A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Upon antigen recognition within peripheral lymphoid organs, B cells interact with T cells and other immune cells to transiently form morphological structures called germinal centers (GCs), which are required for B cells clonal expansion, immunoglobulin class switching, and affinity maturation. This process, known as the GC response, is an energetically demanding process that requires metabolic reprogramming of B cells. Here, we showed that the Ras-related guanosine triphosphate hydrolase (GTPase) R-Ras2 (also known as TC21) plays an essential, nonredundant, and B cellintrinsic role in the GC response. Both the conversion of B cells into GC B cells and their expansion were impaired in mice lacking R-Ras2, but not in those lacking a highly-related R-Ras subfamily member or both the classic H-Ras and N-Ras GTPases. In the absence of R-Ras2, activated B cells did not increase oxidative phosphorylation or aerobic glycolysis. We showed that R-Ras2 was an effector of both the B cell receptor (BCR) and CD40 and that, in its absence, B cells exhibited impaired activation of the PI3K-Akt-mTORC1 pathway, reduced mitochondrial DNA replication, and decreased expression of genes involved in glucose metabolism. Because most human B cell lymphomas originate from GC B cells or B cells that have undergone the GC response, our data suggests that R-Ras2 may also regulate metabolism in B cell malignancies.
Publication Title
R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through a family of Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adapter Card9. Although Card9 complexes are essential for antifungal defense in humans and mice, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, using a proteomic approach, we identified Vav proteins as key activators of the Card9 pathway. Vav1, Vav2 and Vav3 cooperate downstream of Dectin-1, Dectin-2 and Mincle to selectively engage Card9 for NF-?B control and proinflammatory gene transcription but are not involved in MAPK activation. Although Vav family members show functional redundancy, Vav1/2/3 triple-deficient cells are severely impaired for NF-?B and cytokine responses upon stimulation with CLR agonists or hyphae, and Vav1/2/3-/- mice phenocopy Card9-/- animals with extreme susceptibility to fungi and rapid mortality upon Candida albicans infection. In this context, Vav3 is the single most important Vav in mice, and a polymorphism in human VAV3 is associated with susceptibility to candidemia in patients. Our results reveal a molecular mechanism for CLR-mediated Card9 regulation that controls innate immunity to fungal infections. Overall design: RNA profiles of unstimulated or Curdlan-stimulated bone marrow-derived dendritic cells (BMDCs) from wild type (WT) and Vav1/2/3-/- (VAV KO) mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.
Publication Title
Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We analyzed gene expression profiles of myeloma cells belonging to the group of bas prognosis RPMI 8226 and LP1 expressing either the GFP protein or a cyclin D1-GFP fusion protein
Publication Title
Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
Publication Title
Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples