Loss of LOXL2 promotes uterine hypertrophy and tumor progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE213868 | GEO | 2022/09/23
REPOSITORIES: GEO
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Project description:Loss of LOXL2 promotes uterine hypertrophy and tumor progression
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Project description:Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired. 12 samples were analyzed: mES transduced with control shRNA (n=3); mES transduced with LOXL2 shRNA (n=3), ES transduced with control shRNA and treated with RA (n=3); ES transduced with LOXL2 shRNA and treated with RA (n=3)
2015-12-21 | E-GEOD-65675 | biostudies-arrayexpress
Project description:In prostate cancer (PC), cancer-associated fibroblasts (CAFs) exhibit contrasting biological properties to non-malignant prostate fibroblasts (NPFs) and promote tumorigenesis. Resolving intercellular signaling pathways between CAFs and prostate tumor epithelium may offer novel opportunities for research translation. To this end, the proteome and phosphoproteome of four pairs of patient-matched CAFs and NPFs were characterized to identify discriminating proteomic signatures. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a hyper-reaction monitoring data-independent acquisition (HRM-DIA) workflow. Proteins that exhibited a significant increase in CAFs versus NPFs were enriched for the functional categories ‘cell adhesion’ and the ‘extracellular matrix’. The CAF phosphoproteome exhibited enhanced phosphorylation of proteins associated with the ‘spliceosome’ and ‘actin binding’. STRING analysis of the CAF proteome revealed a prominent interaction hub associated with collagen synthesis, modification, and signaling. It contained multiple collagens, including the fibrillar types COL1A1/2 and COL5A1; the receptor tyrosine kinase discoidin domain-containing receptor 2 (DDR2), a receptor for fibrillar collagens; and lysyl oxidase-like 2 (LOXL2), which promotes collagen crosslinking. Increased activity and/or expression of LOXL2 and DDR2 in CAFs were confirmed by enzymatic assays and Western blot analyses. Pharmacological inhibition of CAF-derived LOXL2 perturbed extracellular matrix (ECM) organization and decreased cell migration in wound-healing assays. Furthermore, it significantly impaired the motility of co-cultured RWPE2 prostate tumor epithelial cells. These results indicate that CAF-derived LOXL2 is an important mediator of intercellular communication within the PC tumor microenvironment and a potential therapeutic target.
2019-05-24 | PXD010611 | Pride
Project description:Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired.
2015-12-21 | GSE65675 | GEO
Project description:A novel alternative splicing isoform of LOXL2 â³e13 was expressed ubiquitously in all cell lines and ESCC tissues. In contrast to the impaired deamination enzymatic activity compared with full length LOXL2, LOXL2 â³e13 showed an enhanced ability to promote cell mobility and invasiveness in ESCC cells than full length LOXL2 through a different mechanism. We used cDNA microarrays to identify genes that were differentially expressed upon LOXL2 â³ e13 overexpressed. For this purpose, we selected LOXL2 â³ e13, WT and empty vector control transfeced ESCC KYSE150 cell lines. Total RNA was extracted,compare the gene expression patterns between LOXL2 â³e13, LOXL2 WT and empty vector control transfected cells through the Genechip Primeview Human Gene Expression Array.
2016-07-03 | E-GEOD-53676 | biostudies-arrayexpress
Project description:Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulates endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is up-regulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function. In this dataset we include the global gene expression analysis using exon arrays after silencing LOXL2.
2018-01-24 | GSE107032 | GEO
Project description:A novel alternative splicing isoform of LOXL2 △e13 was expressed ubiquitously in all cell lines and ESCC tissues. In contrast to the impaired deamination enzymatic activity compared with full length LOXL2, LOXL2 △e13 showed an enhanced ability to promote cell mobility and invasiveness in ESCC cells than full length LOXL2 through a different mechanism.
2016-01-01 | GSE53676 | GEO
Project description:Esophageal cancer is the sixth most common cause of cancer death globally, of which esophageal squamous cell carcinoma (ESCC) is the most common histological subtype. High level expression of LOXL2 has been shown to be associated with tumor metastasis and poor clinical outcome in ESCC. To determine whether there are genes whose expression in ESCC cells is regulated by LOXL2, next generation RNA sequencing analysis was used to compare the RNA expression profile of KYSE510 cells before and after silencing LOXL2 expression.
2020-08-01 | GSE135510 | GEO
Project description:Chronic allograft nephropathy (CAN) is a major obstacle in kidney transplantation, often leading to long-term graft failure. Early identification of patients at high risk for CAN could be instrumental to improve outcomes. Here, we investigate Lysyl oxidase ligand 2 (LOXL2) as a predictive biomarker for CAN. Using single cell RNA sequencing of transplant biopsies, immunohistochemistry and immunofluorescence microscopy, we find that LOXL2 labels a distinct intertubular myofibroblast subtype with a smooth muscle actin (SMA)-, CXCL12- and PDGFRb-negative and CD68-positive phenotype. These cells are present in non-fibrotic and fibrotic regions utilizing collagen 3 as scaffold, and are associated with a high expression of extracellular matrix (ECM) proteins and related pathways. Native kidneys also harbor LOXL2+ myofibroblasts, albeit at much lower levels, and their presence correlates with the incidence of chronic kidney disease. Following transplant surgery, LOXL2+ cells can rapidly emerge within days, particularly during episodes of rejection, where they associate with leukocyte aggregates. Notably, elevated cell numbers can be normalized as shown in follow up biopsies. A retrospective analysis of 118 biopsies revealed a significant association between LOXL2+ cell abundance and transplant fibrosis, inflammation, and kidney function. However, no correlation was found with transplant age, rejection type and other Banff parameters. Non-rejecting allografts displayed high variability in the number of LOXL2+ cells, with high abundance serving as a long-term predictor of fibrosis and reduced allograft function. Collectively, our findings suggest that LOXL2+ intertubular cells are a subset of inflammation-associated SMA- myofibroblasts and may be useful as a risk biomarker for early fibrogenesis in non-rejecting allografts.
2025-12-19 | GSE277703 | GEO
Project description:We have identified a new novel spliced variant of Lysyl Oxidase-like 2 (LOXL2), termed LOXL2 delta72, in human oesophageal carcinoma cells (ESCC). To explore the biological function of this variant, the cDNA microarrays was perform to assess the genes expression induced by its over-expression in ESCC KYSE150. We used microarrays to detail the global programmed of genes expression when LOXL2 delta72 over-expressed in KYSE150 cells compared with wild-type LOXL2.
2016-03-28 | GSE53645 | GEO