MITF reprograms the extracellular matrix and focal adhesion in melanoma
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ABSTRACT:
PROVIDER: PRJNA686997 | ENA |
REPOSITORIES: ENA
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Project description:To assess the effects of permanent loss of MITF in melanoma cells, we used the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technique to generate MITF knockout (KO) cell lines in the human hypo-tetraploid SkMel28 melanoma cell line (containing four copies of MITF). We targeted exon 6 (containing the DNA binding domain) of MITF the resulting isogenic cell line is hereafter referred to as ΔMITF-X6. We also performed siRNA mediated transient knock down of MITF along with control siCTRL in 501Mel cells. Furthermore, we used a stable doxycycline inducible over-expression cell line containing FLAG tagged MITF and a control cells with empty vector FLAG in A375P. From our RNA-sequencing studies we found that MITF plays a critical role as a repressor of extracellular matrix gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner.
2020-12-22 | GSE163646 | GEO
Project description: Not available
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Project description:The goal of this study was to identify transcripts, which are differentially regulatulated in the presence and absence of Focal Adhesion Kinase. As Focal Adhesion Kinase activity can depend upon cell density (Snijder et al. Nature 2009), biological replicates where cells, were seeded very sparsely or confluently, were used. Focal Adhesion Kinase Knockout (ATCC CRL-2644) and Rescue Cells (Sieg et al. 1998, clone DA2) were seeded at two different concentrations. Replicas refer to biological replicates, performed on different days. Only one single technical replicate has been done per biological replicate.
2013-09-17 | E-GEOD-43873 | biostudies-arrayexpress
Project description:The goal of this study was to identify transcripts, which are differentially regulatulated in the presence and absence of Focal Adhesion Kinase. As Focal Adhesion Kinase activity can depend upon cell density (Snijder et al. Nature 2009), biological replicates where cells, were seeded very sparsely or confluently, were used.
2013-09-17 | GSE43873 | GEO
Project description:Expression proteomics analysis of focal adhesion complexes isolated from a human immortalized podocyte cell line.
2018-12-14 | PXD010626 | Pride
Project description:Activation of the Wnt pathway is at the core of many human cancers. During canonical Wnt signaling, the Lrp6 and Frizzled receptors bind to the Wnt growth factor, which leads to the complex being endocytosed. Glycogen Synthase Kinase 3 (GSK3), Dishevelled (Dvl), and Axin are sequestered inside the intraluminal vesicles of late endosomes, known as multivesicular bodies (MVBs). Here we present experiments showing that Wnt causes the endocytosis of focal adhesion (FA) proteins and depletion of Integrin β 1 (ITGβ1) from the cell surface. FAs and integrins provide link the cytoskeleton to the extracellular matrix. Wnt-induced macropinocytosis of the plasma membrane caused ITGβ1 depletion and was accompanied by striking changes in the actin cytoskeleton. In situ protease protection assays in cultured cells showed that ITGβ1 was sequestered within membrane-bounded organelles that corresponded to Wnt-induced MVBs containing GSK3 and focal adhesion-associated proteins. An in vivo model using Xenopus embryos dorsalized by Wnt8 mRNA showed that ITGβ1 depletion decreased Wnt signaling. The cross-talk between Wnt signaling, membrane trafficking, and focal adhesions should be relevant to human cancer and cell biology.
2022-03-18 | GSE193381 | GEO
Project description:Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described so far through a hierarchical model in which elements of Hippo pathway are under the control of Focal Adhesions (FAs). Here we unveiled the molecular mechanism by which cell spreading and RhoA GTPase control FA formation through YAP to stabilize the anchorage of actin cytoskeleton to cell membrane. This mechanism required YAP co-transcriptional function and involved the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity led to the modification of cell mechanics, force development, adhesion strength, determined cell shaping, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify Hippo effector as the key determinant of cell mechanics in response to ECM cues.
2017-05-17 | E-MTAB-5217 | biostudies-arrayexpress
Project description:YAP regulates cell mechanics by controlling focal adhesion assembly
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Project description:Cellular senescence is a phenotype characterized by cessation of cell division, which can be caused by exhaustive replication or environmental stress. It is involved in age-related pathophysiological conditions and affects both the cellular cytoskeleton and the prime cellular mechanosensors, focal adhesion complexes. While the size of focal adhesions increases during senescence, it is unknown if and how this is accompanied by a remodeling of the internal focal adhesion structure. Our study uses metal-induced energy transfer to study the axial dimension of focal adhesion proteins from oxidative-stress-induced senescent cells with nanometer precision, and compares these to unstressed cells. We influenced cytoskeletal tension and the functioning of mechanosensitive ion channels using drugs and studied the combined effect of senescence and drug intervention on the focal adhesion structure. We find that H 2 O 2 induced restructuring of the focal adhesion complex indicates a loss of tension and altered talin complexation. Mass spectroscopy-based proteomics confirmed the differential regulation of several cytoskeletal proteins induced by H 2 O 2 treatment.
2023-07-06 | PXD041766 | Pride
Project description:Hypertrophic scar (HTS) formation is characterized by exuberant fibroproliferation for reasons that remain poorly understood1. One important but often overlooked component of wound repair is mechanical force, which regulates reciprocal cell-matrix interactions through focal adhesion components including focal adhesion kinase (FAK)1,2. Here we report that FAK is activated following cutaneous injury and that this activation is potentiated by mechanical loading. Transgenic mice lacking fibroblast-specific FAK exhibit significantly less fibrosis in a preclinical model of HTS formation. Inflammatory pathways involving monocyte chemoattractant protein-1 (MCP-1), a chemokine highly implicated in human skin fibrosis3, are triggered following FAK activation, mechanistically linking physical force to fibrosis. Further, small molecule inhibition of FAK effectively abrogates fibroproliferative mechanisms in human cells and significantly reduces scar formation in vivo. Collectively, these findings establish a molecular basis for HTS formation based on the mechanical activation of fibroblast-specific FAK and demonstrate the therapeutic potential of targeted mechanomodulatory strategies.
2011-01-14 | GSE26390 | GEO