Integrin alpha-V drives pancreatic adenocarcinoma progression due to activation of TGF-β
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE153702 | GEO | 2020/07/31
REPOSITORIES: GEO
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Project description:To explore the dynamics of integrin adhesion complex disassembly, isolated adhesion complexes from U2OS cells were subjected to mass spectrometry based proteomic analysis. U2OS cells were allowed to spread on FN, treated with nocodazole for 4 hours to disrupt microtubules. To coordinate microtubule-induced integrin adhesion complex disassembly nocodazole was subsequently washed out and adhesion complexes isolated at 5, 10 and 15 minutes during this process.
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Project description:Integrin alpha-V drives pancreatic adenocarcinoma progression due to activation of TGF-β
| PRJNA643784 | ENA
Project description:Analysis of gene expression profiles of matrix-detached cells with and without expression of ITGB4, in clustering and non-clustering conditions. The experiment tested the hypothesis that the integrin beta 4 (ITGB4) mediates a significant amount of pro-survival signaling in matrix-detached conditions. Expression of ITGB4 in cancer is correlated with poor patient survival and is impliated in increased metastatic spread. Survival in matrix-deprived conditions is essential to metastasis and targeting signaling downstream of the integrin beta 4 may help curtail metasasis.
2019-04-16 | GSE115059 | GEO
Project description:To explore the dynamics of integrin adhesion complex disassembly, isolated adhesion complexes from U2OS cells were subjected to mass spectrometry based proteomic analysis. U2OS cells were allowed to spread on FN, treated with nocodazole for 4 hours to disrupt microtubules. To coordinate microtubule-induced integrin adhesion complex disassembly nocodazole was subsequently washed out and adhesion complexes isolated at 5, 10 and 15 minutes during this process.
2015-10-14 | PXD002129 | Pride
Project description:Geier2011 - Integrin activation
Rule based model that integrates the available data to test the biololical hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation.
This model is described in the article:
A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
Geier F, Fengos G, Iber D.
PLoS One. 2011;6(11):e24808.
Abstract:
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes.
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2014-03-05 | MODEL1208280001 | BioModels
Project description:Human foreskin fibroblast cells were spread on fibronectin (FN) for 1 h and treated with DMSO or FAK inhibitor (3 uM, AZ13256675 (termed AZ675 for short)) for 1 h. Integrin-associated adhesion complexes isolated from these cells were analysed by mass spectrometry to determine changes in adhesion complex composition upon FAK inhibition. As a negative control, complexes were also isolated from cells attached to transferrin (Tf), which allows integrin-independent adhesion via the transferrin receptor.
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Project description:Human foreskin fibroblast cells were spread on fibronectin (FN) for 1 h and treated with DMSO or FAK inhibitor (3 uM, AZ13256675 (termed AZ675 for short)) for 1 h. Integrin-associated adhesion complexes isolated from these cells were analysed by mass spectrometry to determine changes in adhesion complex composition upon FAK inhibition. As a negative control, complexes were also isolated from cells attached to transferrin (Tf), which allows integrin-independent adhesion via the transferrin receptor.
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Project description:Integrins are among the most abundant cell surface receptors constituting the principal adhesion receptors for the extracellular matrix (ECM), providing a physical anchor for the cell and triggering multiple intracellular signalling events. Loss-of function mutations of the integrin α3 gene (ITGA3) have been recently disclosed in patients with interstitial lung disease, congenital nephrotic syndrome and junctional epidermolysis bullosa, a multiorgan disorder with fatal outcome. In these patients, the respiratory function is strongly impaired and the kidneys are variably affected, whereas skin fragility is rather mild, has a delayed onset after birth or remains unrecognized, suggesting that integrin α3 differently influences the development and homeostasis of these organs. Here we employed authentic human keratinocytes bearing a naturally occurring integrin α3 loss-of-function mutation as a prototype to characterize the molecular mechanisms launched by the constitutional absence of this integrin subunit. To validate our findings, we generated new cellular models, including an additional ILNEB patient cell line, ITGA3 rescued and knockdown cells. We show that keratinocytes lacking a functional α3 subunit have an activated cellular phenotype with a switch in the pattern of integrin α subunits on the cell surface. These assure spreading and adhesion of epidermal keratinocytes but also drive the migratory phenotype of these cells.
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Project description:We identified the SOX4 transcription factor and integrin alpha V encoded by the ITGAV gene as important resistance mechanisms to T cell-mediated cytotoxicity of TNBC cells. Here, we performed RNA seq. analysis of SOX4 and ITGAV deficient (CRISPR knockout) BT549 human and 4T1 murine TNBC cells as compared to control edited counterparts. Additionally, we performed SOX4 specific ChIP-seq studies in BT549 human TNBC cells. The objective of the study was to identify the molecular regulators and signaling pathways that mediate resistance to T cell mediated immunity. GSEA analysis of RNA-seq data showed that the 'interferon response' represented one of the top pathways for genes upregulated in SOX4 or ITGAV edited compared to control TNBC cells. In contrast, gene sets associated with TGF beta and TNF alpha/NF kappa b were negatively enriched in both Sox4 and Itgav edited TNBC cells. Further analysis of RNA-seq data showed that SOX4 or ITGAV edited TNBC cells contained higher mRNA levels of many interferon-stimulated genes (ISGs), including genes associated with important innate immune pathways such as RIG-I/MDA-5, cGAS - STING and the AIM2 inflammasome
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Project description:We identified the SOX4 transcription factor and integrin alpha V encoded by the ITGAV gene as important resistance mechanisms to T cell-mediated cytotoxicity of TNBC cells. Here, we performed RNA seq. analysis of SOX4 and ITGAV deficient (CRISPR knockout) BT549 human and 4T1 murine TNBC cells as compared to control edited counterparts. Additionally, we performed SOX4 specific ChIP-seq studies in BT549 human TNBC cells. The objective of the study was to identify the molecular regulators and signaling pathways that mediate resistance to T cell mediated immunity. GSEA analysis of RNA-seq data showed that the 'interferon response' represented one of the top pathways for genes upregulated in SOX4 or ITGAV edited compared to control TNBC cells. In contrast, gene sets associated with TGF beta and TNF alpha/NF kappa b were negatively enriched in both Sox4 and Itgav edited TNBC cells. Further analysis of RNA-seq data showed that SOX4 or ITGAV edited TNBC cells contained higher mRNA levels of many interferon-stimulated genes (ISGs), including genes associated with important innate immune pathways such as RIG-I/MDA-5, cGAS - STING and the AIM2 inflammasome
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