Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RAC-GEF function as a critical factor in intestinal tumourigenesis

ABSTRACT: RAC-GEF function as a critical factor in intestinal tumourigenesis

PROVIDER: PRJNA445428 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6885294_1.fastq.gz	Fastqsanger.gz
	SRR6885294_2.fastq.gz	Fastqsanger.gz
	SRR6885295_1.fastq.gz	Fastqsanger.gz
	SRR6885295_2.fastq.gz	Fastqsanger.gz
	SRR6885296_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

RAC-GEF function as a critical factor in intestinal tumourigenesis

Project description:Here we investigate the transcription changes in the murine intestine 4 days following loss of APC under the control of Vil-CreErT2 driver. We compare the RNAseq data from epithelial organoids generated from control (APC loss) intestines to organoids generated from lacking VAV2, VAV3 and TIAM1. We show that loss of these GEFs supress the APC WNT driven intestinal phenotype in a RAC-dependent manner.

2019-12-31 | GSE112261 | GEO

A RAC-GEF network critical for early intestinal tumourigenesis.

Project description:RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.

| S-EPMC7782582 | biostudies-literature

RAC-GEF function as a critical factor in intestinal tumourigenesis

Project description:VilCreER APCfl/fl vs VilCreER APCfl/fl, Vav2-/-, Vav3-/-, Tiam1-/-

| PRJEB25520 | ENA

The Rac-GEF Tiam1 controls integrin-dependent neutrophil responses

Project description:Rac GTPases are required for neutrophil adhesion and migration, and for the neutrophil effector responses that kill pathogens. These Rac-dependent functions are impaired when neutrophils lack the activators of Rac, Rac-GEFs from the Prex, Vav and Dock families. In this study, we demonstrate that Tiam1 is also expressed in neutrophils, governing focal complexes, actin cytoskeletal dynamics, polarisation and migration, in a manner depending on the integrin ligand to which the cells adhere. Tiam1 is dispensable for the generation of reactive oxygen species but mediates degranulation and NETs release in adherent neutrophils, as well as the killing of bacteria. In vivo, Tiam1 is required for neutrophil recruitment during aseptic peritonitis and for the clearance of Streptococcus pneumoniae during pulmonary infection. However, Tiam1 functions differently to other Rac-GEFs. Instead of promoting neutrophil adhesion to ICAM1 and stimulating β2 integrin activity as could be expected, Tiam1 restricts these processes. In accordance with these paradoxical inhibitory roles, Tiam1 limits the fMLP-stimulated activation of Rac1 and Rac2 in adherent neutrophils, rather than activating Rac as expected. Tiam1 promotes the expression of several regulators of small GTPases and cytoskeletal dynamics, including αPix, Psd4, Rasa3 and Tiam2. It also controls the association of Rasa3, and potentially αPix, Git2, Psd4 and 14‐3‐3ζ/δ, with Rac. We propose these latter roles of Tiam1 underlie its effects on Rac and β2 integrin activity and on cell responses. Hence, Tiam1 is a novel regulator of Rac-dependent neutrophil responses that functions differently to other known neutrophil Rac-GEFs.

2024-01-26 | PXD046791 | Pride

GEF-H1-IRF5 mediated gene expression changes in BMDM by MDP recognition

Project description:The transcription factor IRF5 is essential for immune defense against pathogens. Here, the authors show that the microtubule-associated factor GEF-H1 plays a critical role in host defense against Listeria monocytogenes in macrophages via activation of the IRF5 kinase IKKe

2019-04-02 | GSE126749 | GEO

Key role for Rac in the early transcriptional response to ECM stiffness and the stiffness-dependent repression of ATF3

Project description:The Rho family GTPases, Rac and Rho, play critical roles in transmitting mechanical information contained within the extracellular matrix (ECM) to the cell. Rac and Rho have well described roles in regulating stiffness-dependent actin remodeling, proliferation and motility. However, much less is known about the relative roles of these GTPases in stiffness-dependent transcription, particularly at the genome-wide level. Here, we selectively inhibited Rac and Rho in mouse embryonic fibroblasts cultured on deformable substrata and used RNA sequencing to elucidate and compare the contribution of these GTPases to the early transcriptional response to ECM stiffness. Surprisingly, we found that the stiffness-dependent activation of Rac is dominant over Rho in the initial transcriptional response to ECM stiffness. We also identified Activating Transcription Factor 3 (ATF3) as a major target of stiffness/Rac-mediated signaling and show that ATF3 repression by ECM stiffness helps to explain how the stiffness-dependent activation of Rac results in the induction of cyclin D1.

2023-10-04 | GSE236266 | GEO

Systemic muscle wasting drives tumourigenesis

Project description:Systemic muscle wasting drives tumourigenesis

| PRJNA587726 | ENA

Hypoxia inhibits HUNK-mediated phosphorylation of GEF-H1 for epithelial-to-mesenchymal transition

Project description:Hypoxia regulates epithelial to mesenchymal transition (EMT) of cancer cells. However, the mechanism underlying hypoxia-mediated EMT remains largely unknow. Here, utilizing colorectal cell carcinoma (CRC) as a model, we find that HUNK inhibits EMT and suppresses metastasis of CRC cells via its substrate GEF-H1 in a kinase-dependent manner. Mechanistically, HUNK directly phosphorylates GEF-H1 at ser645 site, which activates RhoA and consequently leads to a cascade of phosphorylation of LIMK1/CFL-1, thereby stabilizing F-actin and inhibiting EMT. Moreover, hypoxia suppresses HUNK activity and dephosphorylates GEF-H1 to promote EMT. Clinically, the expression levels of both HUNK and phosphorylation of GEH-H1 ser645 are not only downregulated in CRC tissues with metastasis compared to that without metastasis, but also positively correlated among these tissues. Our findings highlight the importance of hypoxia-regulated HUNK kinase activity and phosphorylation of GEF-H1 in regulation of EMT and metastasis of CRC.

2022-05-27 | GSE203440 | GEO

GEF-H1 mediated gene expression changes in BMDCs in response to microtubule destabilization

Project description:GEF-H1 controls transcriptional programs that mediate antitumor immuity upon microtubule destabilization.

2019-10-01 | GSE135264 | GEO

Identification of a mitotic Rac-GEF, Trio, that counteracts MgcRacGAP function during cytokinesis.

Project description:The Rho GTPases RhoA and Rac1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton. RhoA and Rac1 have to be respectively activated and inactivated at the division plane for cytokinesis to occur properly. The inactivation of Rac1 at the cleavage furrow is controlled by MgcRacGAP. However, the guanine-nucleotide exchange factor (GEF) that activates Rac1 during cell division remains unknown. Here, using a siRNA screening approach in HeLa cells, we identify Trio as a mitotic GEF of Rac1. We demonstrate that Trio controls Rac1 activation and subsequent F-actin remodeling in dividing cells. Moreover, Trio depletion specifically rescues the cytokinesis failure induced by MgcRacGAP depletion. Of importance, we demonstrate that this rescue is mediated by the Trio-Rac1 pathway, using GEF-dead mutants of Trio and a specific inhibitor of Rac1 activation by Trio. Overall this work identifies for the first time a GEF controlling Rac1 activation in dividing cells that counteracts MgcRacGAP function in cytokinesis.

| S-EPMC4263449 | biostudies-literature

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