ECT2 promotes proliferation and metastasis of esophageal squamous cell carcinoma（ESCC） via Rho-ERK-VEGF/MMP9 signaling pathway
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PROVIDER: PRJNA576427 | ENA |
REPOSITORIES: ENA
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Project description:In order to analyze the difference in the whole gene expression profile of ESCC(esophageal squamous cell carcinoma) and normal adjecent esophageal tissue as well as cancer metastasis tissue. We found that ECT2 (Epithelial cell transformation sequence 2) is highly expressed in esophageal squamous cell carcinoma compared with adjacent normal tissues by microarray analysis, and we further analyzed the expression of ECT2 in 40 patients by qRT-PCR, and found that ECT2 is indeed high in cancer tissues. Expressed in normal tissues adjacent to cancer. We first confirmed the overexpression of ECT2 in ESCC, further confirming the signaling pathway in the oncogenisis of ESCC.
2022-07-08 | GSE138570 | GEO
Project description:Epithelial Cell Transforming Sequence 2 (ECT2), a guanine nucleotide exchange factor (GEF) for Rho GTPases, is overexpressed in many cancers and is involved in signal transduction pathways that promote cancer cell proliferation, invasion and tumorigenesis. Recently, we demonstrated that a significant pool of ECT2 localizes to the nucleolus of non small cell lung cancer (NSCLC) cells where it binds the transcription factor Upstream Binding Factor 1 (UBF1) on the promoter regions of the ribosomal DNA (rDNA) and activates rDNA transcription, transformed growth and tumor formation. Here we investigate the mechanism by which ECT2 engages UBF1 on rDNA. Mutagenesis of ECT2 demonstrates that the tandem BRCT domain of ECT2 mediates binding to UBF1. Biochemical and mass spectrometry analysis reveals that Protein Kinase Ci (PKCi) directly phosphorylates UBF1 at Ser412 to generate a phosphopeptide binding epitope that binds the ECT2 BRCT domain. Lentiviral shRNA knockdown and reconstitution experiments demonstrate that both a functional ECT2 BRCT domain and the UBF1 Ser412 phosphorylation site are required for UBF1 mediated ECT2 recruitment to rDNA, elevated rRNA synthesis and transformed growth. Taken together, our study provides new molecular insight into ECT2 mediated regulation of rDNA transcription in cancer cells and provides a rationale for therapeutic targeting of UBF1 and ECT2 stimulated rDNA transcription for the treatment of NSCLC.
2020-04-10 | MSV000085269 | MassIVE
Project description:Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype and the lack of specific signature makes difficult the development of targeted therapeutic strategy. We previously found that PRICKLE1, an evolutionary conserved protein acting as a regulator of vertebrate development, is upregulated in TNBC. Proteomic approaches allowed us to decipher the protein complex associated to PRICKLE1 in TNBC. Within that complex, we identified a large subset of proteins involved in the regulation of Rho-GTPase family members. We build a metagene with regulators of small G-protein activity and we found that this metagene is overexpressed in TNBC and is a poor prognosis marker. We analyzed the combination of the metagene expression and PRICKLE1 expression and identified that combined expression of ECT2 and PRICKLE1 provides a worst prognosis than PRICKLE1 expression alone in TNBC. ECT2 is a GEF for Rac1 and we showed that PRICKLE1 regulate the enzymatic activity of ECT2. Finally, we also observed that Ect2 and Prickle1 are functionally connected during evolution since both act synergistically to coordinate cellular movement during vertebrate gastrulation. Our results demonstrate the pivotal role of PRICKLE1 in TNBC and build the path for development of targeted therapeutic strategies to heal TNBC patients.
2019-10-15 | PXD011253 | Pride
Project description:Proliferation of heart muscle cells (cardiomyocytes) is the basis for heart development and regeneration. In mammals, cardiomyocytes become binucleated, which is thought to limit their proliferative capacity, but mechanisms are unknown. Here, we show the detailed mechanisms of formation of binucleated cardiomyocytes and how these mechanisms are dysregulated in congenital heart disease (CHD). Cardiomyocytes become binucleated by failing the last stage of cytokinesis, abscission. We identified the underlying molecular mechanism with single-cell transcriptional profiling, which showed repression of the cytokinesis gene Ect2, a Rho-guanine-nucleotide exchange factor. Inactivating Ect2 tripled the proportion of binucleated cardiomyocytes and reduced the number of cardiomyocytes by 34% in newborn mice, which was lethal. Cardiomyocyte-specific overexpression of Ect2 in transgenic mice decreased cytokinesis failure. We demonstrate that the Ect2 gene is regulated by the Hippo tumor suppressor pathway, and upstream of that, by β-adrenergic receptor signaling. In neonatal mice, stimulating β-adrenergic signaling pathway output with forskolin decreased the number of cardiomyocytes, and administration of β-blockers increased the number of cardiomyocytes. Finally, we show that patients with tetralogy of Fallot with pulmonary stenosis (ToF/PS), a common type of CHD, develop a 2.2-fold increase in bi- and multi-nucleated cardiomyocytes. Using in vivo labeling of one ToF/PS patient with 15N-thymidine, followed by imaging mass spectrometry, we demonstrate that this increase happens after birth. Organotypic cultures of myocardium from infants with ToF/PS showed that cardiomyocyte binucleation could be reduced with β-blockers. These results demonstrate how cardiomyocyte proliferation stops and provide the basis for new therapeutic strategies to increase cardiomyocyte proliferation in patients with CHD.
2019-09-30 | GSE108359 | GEO
Project description:RNA-seq of WT (Col-0) and ect2 to study the differentially expressed genes.
2018-06-21 | GSE108118 | GEO
Project description:To understand the difference of protein expression between paired esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues, we collected 10 paired ESCC and normal tissues from surgical resected specimems for high-throughput proteomic experiments. From comparative analysis, the dysregulated signaling pathways in ESCC could be uncovered.
2020-08-11 | PXD019834 | Pride
Project description:To discover ESCC related proteins, we used SWATH to quantify the protein abundance between ESCC and adjacent tissues. Briefly, we pooled 10 ESCCtissues and their corresponding adjacent tissues for SWATH acquisition with three replicates.Three DDA repeats were also acquired with the pooled 10-paired ESCC tissue.The trypsin digested peptide mixture was analyzed by AB SCIEX 5600 (AB SCIEX).The database searching procedure was achieved using ProteinPilot v4.5 (AB Sciex). The database is IPI_homo_sapiens_V3.87.
2015-09-22 | PXD001764 | Pride
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:As microRNAs have emerged as important regulators of molecular events occurring at the synapses, new questions about their regulatory effect on the behavior have arisen. In the present study, we elucidated the physiological consequences of miR132-Mmp9 mRNA interaction in vivo. To address this question, we created a new mouse model with a disrupted miR132 binding site in Mmp9 mRNA 3’UTR. In the current manuscript, we show for the first time that the dysregulated specific targeting of miR132 to Mmp9 mRNA in the mouse brain results in the increased level of Mmp9, which affects synaptic plasticity and has an effect on mice behavior. Our data points at the importance of complex and precise regulation of Mmp9 level by miR132 in the brain.
2025-03-07 | GSE190716 | GEO
Project description:RNA sequencing of HUVECs stimulated with VEGF, OSM+VEGF, or CNTF+CNTFR+VEGF
| PRJNA807293 | ENA