SMARCA4 Inhibits Breast Tumor progression through Transcriptional Activation of GTPase Activating Factor ARHGAP29 and RHOA Suppression [RNA]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1086790 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The chromatin-remodeling SWI/SNF complex emerged as a potent suppressor of tumor spheroid growth. SMARCA4 was identified as a top candidate to suppress TNBC growth in 3D tumor spheroid model using genome-wide CRISPR screen. Specifically, the loss of the SWI/SNF ATPase subunit SMARCA4 promotes tumor spheroid growth with reduced compactness, and enhanced the growth in breast primary tumors and metastasis across multiple breast cancer models. Further investigations revealed its function in inhibiting the RHOA pathway. SMARCA4 is required for the transcription of Rho GTPase activating factor ARHGAP29, achieved through direct binding to its promoter to provide DNA accessibility. The loss of SMARCA4 resulted in reduced ARHGAP29 levels and hyperactive RHOA signaling. This subsequently disrupted cell adhesion, facilitated a loose spheroid structure and promoted spheroid growth.
2025-02-12 | GSE261369 | GEO
Project description:The chromatin-remodeling SWI/SNF complex emerged as a potent suppressor of tumor spheroid growth. SMARCA4 was identified as a top candidate to suppress TNBC growth in 3D tumor spheroid model using genome-wide CRISPR screen. Specifically, the loss of the SWI/SNF ATPase subunit SMARCA4 promotes tumor spheroid growth with reduced compactness, and enhanced the growth in breast primary tumors and metastasis across multiple breast cancer models. Further investigations revealed its function in inhibiting the RHOA pathway. SMARCA4 is required for the transcription of Rho GTPase activating factor ARHGAP29, achieved through direct binding to its promoter to provide DNA accessibility. The loss of SMARCA4 resulted in reduced ARHGAP29 levels and hyperactive RHOA signaling. This subsequently disrupted cell adhesion, facilitated a loose spheroid structure and promoted spheroid growth.
2025-02-12 | GSE261368 | GEO
Project description:SMARCA4 Inhibits Breast Tumor progression through Transcriptional Activation of GTPase Activating Factor ARHGAP29 and RHOA Suppression [ATAC]
| PRJNA1086794 | ENA
Project description:Rho family small GTPases serve as molecular switches in the regulation of diverse cellular functions including actin cytoskeleton remodeling, cell migration, gene transcription, and cell proliferation. Importantly, Rho overexpression is frequently seen in many carcinomas. However, published studies have almost invariably utilized immortal or tumorigenic cell lines to study Rho GTPase functions and there are no studies on the potential of Rho small GTPase to overcome senescence checkpoints and induce preneoplastic transformation of human mammary epithelial cells (hMECs). We found that ectopic expression of wild-type RhoA as well as a constitutively-active RhoA mutant (G14V) in primary hMEC strains led to their immortalization and preneoplastic transformation. Significantly, RhoA-T37A mutant, known to be incapable of interacting with many well known Rho-effectors ,was also capable of immortalizing hMECs.Our results demonstrate that RhoA can induce the preneoplastic transformation of hMECs by altering multiple pathways linked cellular transformation and breast cancer. Through microarray analysis, we want to identify genes and pathways linked to RhoA induced hMECs immortalization. Experiment Overall Design: 4 samples, in triplicate analyses per sample.
2008-10-26 | E-GEOD-12917 | biostudies-arrayexpress
Project description:Rho family small GTPases serve as molecular switches in the regulation of diverse cellular functions including actin cytoskeleton remodeling, cell migration, gene transcription, and cell proliferation. Importantly, Rho overexpression is frequently seen in many carcinomas. However, published studies have almost invariably utilized immortal or tumorigenic cell lines to study Rho GTPase functions and there are no studies on the potential of Rho small GTPase to overcome senescence checkpoints and induce preneoplastic transformation of human mammary epithelial cells (hMECs). We found that ectopic expression of wild-type RhoA as well as a constitutively-active RhoA mutant (G14V) in primary hMEC strains led to their immortalization and preneoplastic transformation. Significantly, RhoA-T37A mutant, known to be incapable of interacting with many well known Rho-effectors ,was also capable of immortalizing hMECs.Our results demonstrate that RhoA can induce the preneoplastic transformation of hMECs by altering multiple pathways linked cellular transformation and breast cancer. Through microarray analysis, we want to identify genes and pathways linked to RhoA induced hMECs immortalization.
2008-09-26 | GSE12917 | GEO
Project description:FoxM1 activates genes that regulate S-G2-M cell-cycle progression and, when overexpressed, is associated with poor clinical outcome in multiple cancers. Here we identify FoxM1 as a tumor suppressor in mice that, through its N-terminal domain, binds to and inhibits Ect2 to limit the activity of RhoA GTPase and its effector mDia1, a catalyst of cortical actin nucleation. FoxM1 insufficiency impedes centrosome movement through excessive cortical actin polymerization, thereby causing the formation of non-perpendicular mitotic spindles that missegregate chromosomes and drive tumorigenesis in mice. Importantly, low FOXM1 expression correlates with RhoA GTPase hyperactivity in multiple human cancer types, indicating that suppression of the newly discovered Ect2-RhoA-mDia1 oncogenic axis by FoxM1 is clinically relevant. Furthermore, by dissecting the domain requirements through which FoxM1 inhibits Ect2 GEF activity, we provide mechanistic insight for the development of pharmacological approaches that target protumorigenic RhoA activity.
2020-07-09 | GSE130410 | GEO
Project description:Differential protein expression between RhoA ko and wt bone marrow-derived dendritic cells
2015-10-01 | PXD001636 | Pride
Project description:Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive lymphoid tumor derived from malignant transformation of T follicular helper (Tfh) cells. Genetically, AITL is characterized by loss of function mutations in the Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val, G17V) in the RHOA small GTPase gene Moreover, RHOA G17V expression in Tet2 deficient hematopoietic progenitors resulted in the specific development of lymphoid tumors resembling human AITL. Notably, inhibition of ICOS signaling impaired the growth of RHOA G17V-induced mouse lymphomas in vivo, thus providing a potential new rational approach for the treatment of AITL.
2018-10-01 | GSE83918 | 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:Oligodendrocyte differentiation and subsequent myelination rely on strict regulatory mechanisms and molecules. Here we aimed at understanding the role of the Rho GTPase RhoA during oligodendrocyte differentiation and myelination in vivo. Using a conditional cell-specific ablation of Rhoa (Rhoa fl/fl mice crossed with Cnp-Cre mice) in oligodendrocytes, we show that RhoA controls the timing and progression differentiation and myelination. To identify putative mechanisms underlying the Rhoa cKO phenotype, we performed quantitative label-free LC-MS/MS proteomics on optic nerves from Rhoa cKO (Rhoa fl/fl Cre+) and control mice (Rhoa fl/fl Cre-) at 30 days post-birth (P30). Manual annotation of the differentially abundant proteins showed a large modulation of several proteins clusters associated with actin cytoskeleton, signal transduction and mitochondria.
2024-11-05 | PXD055052 | Pride