Expression data from actomyosin contractility regulated genes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Chris Marshall
PROVIDER: E-GEOD-23764 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Actomyosin contractility regulates cell morphology and movement. The objective of this study was to identify whether actomyosin contractility regulates gene expression in tumour cells and whether such genes are involved in cell morphology and movement. Gene expression analysis was carried out on highly contractile melanoma cell line A375M2 plated on a deformable collagen matrix under conditions where actomyosin contractility could be altered following treatment with blebbistatin, a direct inhibitor of myosin II, or Rho-kinase inhibitors Y27632 or H1152 that interfere with signalling to myosin II.
2010-08-24 | GSE23764 | GEO
Project description:The fibroblast-populated 3D collagen matrix has been used to study the effect of mechanical stress on cell fate; this process is relevant to the fields of wound healing and tissue engineering. Gene array data was generated from mechanically stressed vs. stress-released matrices. The parameters of the collagen matrix model were: collagen type = bovine type I; collagen concentration = 1.5 mg/mL; initial matrix volume = 0.2 mL; initial matrix diameter = 11 mm (cultured in 24-well plates); cell type = human foreskin fibroblast, passage <10; initial matrix cell concentration = 1,000,000 cell/mL (200,000 cell/matrix); culture medium = 5% FBS in DMEM with 1 M-BM-5g/mL ascorbate. Matrices (n = 6 per experimental group) were incubated for 24 hr in the attached state; the released groups then underwent matrix detachment from the culture plate (defined as t = 0), while the attached groups were left undisturbed. RNA was isolated from attached and released matrices 6 and 24 hr after t = 0. Gene expression in the attached vs. released condition at 6 or 24 hr then was analyzed by hybridizing the anti-sense RNA derived from attached and released matrices at a given time point onto a single chip. Refer to the attached Figure 1 for the experimental design. The index experiment was defined as the comparison of gene expression in attached vs. released collagen matrices in a single strain of human foreskin fibroblasts at 6 and 24 hr after stress-release (i.e., after t = 0). Each experiment utilized two mechanical conditions (attached and released) at two time points (6 and 24 hr). So with each condition utilizing 6 matrices, each index experiment required a total of 24 matrices. In each index experiment, the chip hybridizations were: (i) 6 hr attached vs. 6 hr released, and (ii) 24 hr attached vs. 24 hr released (i.e., two gene chips per index experiment). Each hybridization was done using a 10K spotted gene chip manufactured in the UNMC Microarray Core Facility. The index experiment was performed on three fibroblast strains, meaning that expressional data was derived from three foreskin donors (nonpooled samples). Dye-swap was not performed; dye assigned to attached vs. released remained constant among all chips. Since the index experiment was performed three times, the total number of gene chips used for this entire dataset was six.
2012-07-19 | E-GEOD-39475 | biostudies-arrayexpress
Project description:To understand how mechanical cues regulate cell metabolism, we compared early changes in gene expression in Ras-transformed MCF10AtK1 mammary epithelial cells grown in high cytoskeletal tension conditions (plastics) vs. cells grown in low cytoskeletal tension conditions (inhibition of the non-muscle myosin II regulatory kinases ROCK and MLCK with standard small-molecule inhibitors Y27632 and ML7, respectively). Keywords: Expression profiling by array
2019-02-05 | GSE107275 | GEO
Project description:Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, is poorly understood. The role of RhoA GTPase-mediated contractile activity, cell adhesive interactions, and gene expression in regulation of aqueous humor outflow was investigated using adenoviral vector-driven expression of constitutively active RhoA (RhoAV14). Organ cultured anterior segments from porcine eyes expressing RhoAV14 exhibited significant reduction of aqueous humor outflow. Cultured TM cells expressing RhoAV14 revealed strong contractile cell morphology, increased actin stress fibers and focal adhesions, along with increased levels of phosphorylated myosin II, and collagen IV, fibronectin and laminin. cDNA microarray analysis of RNA extracted from RhoAV14 expressing human TM cells revealed a significant increase in the expression of genes encoding extracellular matrix (ECM) proteins, cytokines, integrins, cytoskeletal proteins and signaling proteins. Conversely, various ECM proteins stimulated robust increases in phosphorylation of myosin II, paxillin and focal adhesion kinase, and activated Rho GTPase and actin stress fiber formation in TM cells, indicating a potential regulatory feedback interaction between ECM-induced mechanical strain and Rho GTPase-induced isometric tension in TM cells. Collectively, these data demonstrate that sustained activation of Rho GTPase signaling in the aqueous humor outflow pathway increases resistance to aqueous humor outflow through the trabecular pathway by influencing the contractile force, cell adhesive interactions, and the expression of ECM proteins and cytokines in TM cells. Keywords: Gene Expression Two condition experiment: Human trabecular mesh work cells infected with Adenivirus expressing GFP Vs Adenovirus expressing GFP and constitutively active RhoAV14
2010-05-19 | E-GEOD-9288 | biostudies-arrayexpress
Project description:Tissue morphogenesis requires the spatial control over actomyosin contractility to drive cell shape changes. How developmental patterning information controls cell mechanics is poorly understood. In the Drosophila embryo ectoderm, Myosin-II is enriched at the interface between antero-posterior neighboring cells, leading to planar polarized cell intercalation. G protein-coupled receptors (GPCRs) are required for planar polarized Myosin-II activation at junctions and Toll receptors provide a positional code underlying this process. How Toll receptors polarize actomyosin contractility remains unknown. Here we report that cells expressing different levels of a single Toll receptor Toll-8 activate Myosin-II at their interface. Surprisingly, the Toll-8 intracellular domain is not required for signaling at cell interfaces suggesting signaling by proxy. We found that Toll-8 forms a molecular complex with the adhesion GPCR Cirl/Latrophilin that is required for Toll-8 dependent junctional Myosin-II activation. Strikingly, the interfaces between Cirl expressing and cirl mutant cells also activate Myosin-II suggesting that Toll-8 induces Cirl asymmetric signaling at cell interfaces. We further showed that Toll-8 recruits Cirl both in trans and in cis, inducing asymmetric Cirl localization at the boundary of the Toll-8 expression domain. Finally, we found that Toll-8 and Cirl exhibit dynamic interdependent planar polarization when neighboring cells express different levels of Toll-8. Through this feedback, Toll-8 and Cirl self-organize planar polarized signaling.
2021-04-22 | PXD017895 | Pride
Project description:MASTL (Microtubule associated serine-threonine kinase-like) is a relatively recently identified mitotic accelerator. There are also indications of its role in cancer progression, especially in breast cancer, but the molecular mechanisms behind this and the cell cycle independent functions of MASTL are poorly understood. Regulation of cell adhesion and actin dynamics play a central role in governing cell contractility, migration and cell division in normal and cancer cells. Here, we identify MASTL as regulator of cell contractility and activator of the transcriptional co-activator MTRF-A. We show that depletion of MASTL increases cell contact with the extracellular matrix, reduces contractile actin stress fibers in normal and breast cancer cells. Importantly, depletion of MASTL also leads to strongly impairs motility of breast cancer cells. Our transcriptome and proteome profiling revealed that depletion of MASTL impairs transcription and expression of several MRTF-A target genes implicated in cellular movement and actomyosin contraction, including Rho Guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and tropomyosin 4.2 (TPM4). Mechanistically, we find that MASTL is necessary for serum-induced activation of SRF/MTRF-A transcription and that exogenous expression of GEF-H1 in MASTL depleted cells is sufficient to restore cell contractility. Taken together, our results suggest that MASTL is a previously undescribed key regulator of cell morphology and the actin cytoskeleton through transcriptional control of multiple adhesion and actin cytoskeleton regulating genes with key roles in contractility, cell adhesion and migration. MASTL (Microtubule associated serine-threonine kinase-like) is a relatively recently identified mitotic accelerator. There are also indications of its role in cancer progression, especially in breast cancer, but the molecular mechanisms behind this and the cell cycle independent functions of MASTL are poorly understood. Regulation of cell adhesion and actin dynamics play a central role in cell migration, morphology and cancer progression, but the role of MASTL in these processes has not been evaluated. Here, we show that depletion of MASTL increases cell contact with the extracellular matrix in breast cancer cells. Importantly, depletion of MASTL also leads to reduction of contractile actin stress fibers and decreased cell motility. Further, our transcriptome and proteome profiling revealed that mechanistically depletion of MASTL impairs transcription and expression of regulators of cellular movement and actomyosin contraction, including Rho Guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and tropomyosin 4.2 (TPM4). Further, we show that the transcriptional changes are caused by defectiveness of the serum response factor (SRF) signalling. Importantly, this study reveals advanced role for MASTL in interphase cells that activates a transcriptional program strongly impacting on the expression of regulators of cellular motility and actomyosin contraction.
2020-04-14 | PXD013757 | Pride
Project description:The effect of short term (24h and 48h) silencing of MASTL for total transcriptome was studied in human breast cancer cell line (MDA-MB-231). Microtubule-associated serine/threonine-protein kinase-like (MASTL) is a mitosis-accelerating kinase with emerging roles in cancer progression. However, possible cell cycle–independent mechanisms behind its oncogenicity remain ambiguous. Here, we identify MASTL as an activator of cell contractility and MRTF-A/SRF (myocardin-related transcription factor A/serum response factor) signaling. Depletion of MASTL increased cell spreading while reducing contractile actin stress fibers in normal and breast cancer cells and strongly impairing breast cancer cell motility and invasion. Transcriptome and proteome profiling revealed MASTL-regulated genes implicated in cell movement and actomyosin contraction, including Rho guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and MRTF-A target genes tropomyosin 4.2 (TPM4), vinculin (VCL), and nonmuscle myosin IIB (NM-2B, MYH10). Mechanistically, MASTL associated with MRTF-A and increased its nuclear retention and transcriptional activity. Importantly, MASTL kinase activity was not required for regulation of cell spreading or MRTF-A/SRF transcriptional activity. Taken together, we present a previously unknown kinase-independent role for MASTL as a regulator of cell adhesion, contractility, and MRTF-A/SRF activity.
2020-04-14 | GSE131833 | GEO
Project description:Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, is poorly understood. The role of RhoA GTPase-mediated contractile activity, cell adhesive interactions, and gene expression in regulation of aqueous humor outflow was investigated using adenoviral vector-driven expression of constitutively active RhoA (RhoAV14). Organ cultured anterior segments from porcine eyes expressing RhoAV14 exhibited significant reduction of aqueous humor outflow. Cultured TM cells expressing RhoAV14 revealed strong contractile cell morphology, increased actin stress fibers and focal adhesions, along with increased levels of phosphorylated myosin II, and collagen IV, fibronectin and laminin. cDNA microarray analysis of RNA extracted from RhoAV14 expressing human TM cells revealed a significant increase in the expression of genes encoding extracellular matrix (ECM) proteins, cytokines, integrins, cytoskeletal proteins and signaling proteins. Conversely, various ECM proteins stimulated robust increases in phosphorylation of myosin II, paxillin and focal adhesion kinase, and activated Rho GTPase and actin stress fiber formation in TM cells, indicating a potential regulatory feedback interaction between ECM-induced mechanical strain and Rho GTPase-induced isometric tension in TM cells. Collectively, these data demonstrate that sustained activation of Rho GTPase signaling in the aqueous humor outflow pathway increases resistance to aqueous humor outflow through the trabecular pathway by influencing the contractile force, cell adhesive interactions, and the expression of ECM proteins and cytokines in TM cells. Keywords: Gene Expression
2008-09-25 | GSE9288 | GEO
Project description:Cen3tel cells, obtained by telomerase immortalization of human fibroblasts, gradually underwent neoplastic transformation and became metastatic in immunocompromised mice. Neoplastic transformation was associated with a change in cell morphology (from fibroblastic to polygonal). Tumorigenic cells acquired a clear-cut membrane localization of adhesion molecules, a reorganization of the actin cytoskeleton, increased cell motility and invasiveness. In a 3-dimensional environment, tumorigenic cells showed a spherical morphology with cortical actin rings, suggesting a switch from a mesenchymal to an amoeboid ROCK-dependent movement. Accordingly, cell invasion decreased upon treatment with the ROCK inhibitor Y27632, but not with the matrix protease inhibitor Ro28-2653. The increased invasiveness of tumorigenic cen3tel cells was associated with a reduced expression of RhoE, a cellular inhibitor of ROCK. Ectopic RhoE expression decreased cen3tel invasion capability. These results point to RhoE and ROCK as regulators of invasiveness of mesenchymal tumor cells and indicate ROCK as a possible therapeutic target.
2011-04-20 | GSE15742 | GEO
Project description:To evaluate changes in gene expression in MDA-MB-231 cancer cells upon interaction with different extracellular matrices Gene expression in MDA-MB-231 cells was assayed after overnight incubation of the cells on gelatin or dense fibrillar collagen (HDFC) matrices at the presence or absence of serum in tissue culture medium. Five repeats were performed
2015-01-16 | E-GEOD-53104 | biostudies-arrayexpress