Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA141413 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and a frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl- Oxidase-Like 2 (LOXL2) as an EMT player and a poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Identification of new molecular markers in basal breast carcinomas 58 (IDC) infiltrative breast ductal carcinoma samples (Grade 3)
2011-10-20 | E-GEOD-29581 | biostudies-arrayexpress
Project description:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and a frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl- Oxidase-Like 2 (LOXL2) as an EMT player and a poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Identification of new molecular markers in basal breast carcinomas
2011-10-21 | GSE29581 | GEO
Project description:Primary murine lung fibroblasts were transfected with either control (scrambled) or sequence-specific siRNA against Lysyl oxidase (Lox), Lysyl oxidase-like (Loxl1) or Lysyl oxidase-like 2 (Loxl2) genes. Cells were harvested 48 hours after the transfection. Multiple changes in gene expression were found in the corrected p values in this microarray study.
2016-10-25 | GSE89121 | GEO
Project description:Epithelial-to-Mesenchymal Transition (EMT) is a key process contributing to the aggressiveness of cancer cells. EMT is triggered by activation of different transcription factors collectively known as EMT-TFs. Different cellular cues and cell signalling networks activate EMT at transcriptional and posttranscriptional level in different biological and pathological situations. Among them, overexpression of LOXL2 (lysyl oxidase-like 2) induces EMT independent of its catalytic activity. Remarkably, perinuclear/cytoplasmic accumulation of LOXL2 is a poor prognosis marker of squamous cell carcinomas and is associated to basal breast cancer metastasis by mechanisms no yet fully understood. Here, we report that overexpression of LOXL2 promotes its accumulation in the Endoplasmic Reticulum where it interacts with HSPA5 leading to activation of the IRE1-XBP1-branch of the Unfolded Protein Response (UPR). LOXL2-dependent UPR activation induces the expression of several EMT-TFs: SNAI1, SNAI2, ZEB2 and TCF3 that are direct transcriptional targets of XBP1. Remarkably, inhibition of IRE1 blocks LOXL2-dependent upregulation of EMT-TFs thus hindering EMT induction. LOXL2 relationship to Endoplasmic Reticulum Stress
2017-05-11 | GSE90605 | GEO
Project description:Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion. Microarray analysis was performed using GeneChip technology in EVCTs isolated from first trimester human placentae. Gene expression in rosiglitazone-treated primary EVCT cultures was compared with matched untreated controls. A total of 175 probe sets identified differentially regulated genes. One of these genes, lysyl oxidase (LOX) which was up-regulated, was further analyzed. Expression of the LOX family was determined by real time Q-PCR, Western blotting, immunohistochemistry and immunofluorescence. LOX, LOXL and LOXL2 mRNA expression was significantly upregulated in PPARg-activated EVCTs. LOX and LOXL2 protein were present throughout the trophoblast cytoplasm, while LOXL was localized to the nucleus and nucleolus. Cell invasion assays on Matrigel Transwells showed that specific inhibition of LOX activity by M-CM-^_-aminopropionitrile led to an increase in EVCT invasiveness, showing the basal inhibitory effect of LOX and LOX-like in the trophoblastic cells invasion process. Together these results show that LOX family as PPARg-target genes participate to the regulation of trophoblast invasion. Total RNA from EVCT were labelled according to the standard Affymetrix protocol. Five independent targets per treatment vs control were generated and hybridized on a GeneChip.
2013-12-04 | E-GEOD-28426 | biostudies-arrayexpress
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
Project description:Human placental development is characterized by invasion of extravillous cytotrophoblasts (EVCTs) into the uterine wall during the first trimester of pregnancy. Peroxisome proliferator-activated receptor gamma (PPARG) plays a major role in placental development, and activation of PPARG by its agonists results in inhibition of EVCT invasion in vitro. To identify PPARG target genes, microarray analysis was performed using GeneChip technology on EVCT primary cultures obtained from first-trimester human placentas. Gene expression was compared in EVCTs treated with the PPARG agonist rosiglitazone versus control. A total of 139 differentially regulated genes were identified, and changes in the expression of the following 8 genes were confirmed by reverse transcription-quantitative polymerase chain reaction: a disintegrin and metalloproteinase domain12 (ADAM12), connexin 43 (CX43), deleted in liver cancer 1 (DLC1), dipeptidyl peptidase 4 (DPP4), heme oxygenase 1 (HMOX-1), lysyl oxidase (LOX), plasminogen activator inhibitor 1 (PAI-1) and PPARG. Among the upregulated genes, lysyl oxidase (LOX) was further analyzed. In the LOX family, only LOX, LOXL1 and LOXL2 mRNA expression was significantly upregulated in rosiglitazone-treated EVCTs. RNA and protein expression of the subfamily members LOX, LOXL1 and LOXL2 were analyzed by absolute RT-qPCR and western blotting, and localized by immunohistochemistry and immunofluorescence-confocal microscopy. LOX protein was immunodetected in the EVCT cytoplasm, while LOXL1 was found in the nucleus and nucleolus. No signal was detected for LOXL2 protein. Specific inhibition of LOX activity by beta-aminopropionitrile in cell invasion assays led to an increase in EVCT invasiveness. These results suggest that LOX, LOXL1 and LOXL2 are downstream PPARG targets and that LOX activity is a negative regulator of trophoblastic cell invasion. Microarray analysis was performed using GeneChip technology in EVCTs isolated from first trimester human placentae. Gene expression in rosiglitazone-treated primary EVCT cultures was compared with matched untreated controls. A total of 175 probe sets identified differentially regulated genes. One of these genes, lysyl oxidase (LOX) which was up-regulated, was further analyzed. Expression of the LOX family was determined by real time Q-PCR, Western blotting, immunohistochemistry and immunofluorescence. LOX, LOXL and LOXL2 mRNA expression was significantly upregulated in PPARg-activated EVCTs. LOX and LOXL2 protein were present throughout the trophoblast cytoplasm, while LOXL was localized to the nucleus and nucleolus. Cell invasion assays on Matrigel Transwells showed that specific inhibition of LOX activity by ß-aminopropionitrile led to an increase in EVCT invasiveness, showing the basal inhibitory effect of LOX and LOX-like in the trophoblastic cells invasion process. Together these results show that LOX family as PPARg-target genes participate to the regulation of trophoblast invasion.
2013-12-04 | GSE28426 | GEO
Project description:Oxidation of histone H3 at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase–like 2 (LOXL2). This histone modification is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells and has been linked to the maintenance of compacted chromatin. However, the molecular mechanism underlying this maintenance is still unknown. Here we show that LOXL2 interacts with RUVBL1, RUVBL2, BAF53, and DMAP1, a complex involved in the incorporation of the histone variant H2A.Z. Our experiments indicate that this interaction and the active form of RUVBL2 are required to maintain LOXL2-dependent chromatin compaction. Genome-wide experiments showed that H2A.Z, RUVBL2, and H3K4ox colocalize in heterochromatin regions. In the absence of LOXL2 or RUVBL2, global levels of the heterochromatin histone mark H3K9me3 were strongly reduced, and the ATAC-seq signal in the H3K9me3 regions was increased. Finally, we observed that the interplay between these series of events is required to maintain H3K4ox-enriched heterochromatin regions, which in turn is key for maintaining the oncogenic properties of the TNBC cell line tested (MDA-MB-231).
2023-12-31 | GSE142463 | GEO
Project description:Matrix stiffening by lysyl oxidase-like 2 (LOXL2) mediated collagen cross-linking is proposed as a core feed-forward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested targeting LOXL2 may not have disease relevance, however target engagement was not directly evaluated. We compared the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to determine the model with greatest disease relevance. Within the selected model system, we then evaluated AB0023, identifying that it did not inhibit collagen cross-linking or reduce tissue stiffness, nor did it inhibit LOXL2 catalytic activity. In contrast it did potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking or tissue stiffening. These findings have implications for the interpretation of lack of efficacy of simtuzumab in clinical trials of fibrotic diseases.
2024-02-19 | GSE255705 | GEO
Project description:The transcription factor GATA3 is essential for luminal cell differentiation during mammary gland development and critical for formation of the luminal subtypes of breast cancer. Ectopic expression of GATA3 promoted global alterations of the transcriptome of basal triple-negative breast cancer cells resulting in molecular and cellular changes associated with a more differentiated, luminal tumor subtype and a concomitant reduction in primary tumor growth, lung metastasis, and macrophage recruitment at the metastatic site. Importantly, we demonstrate that the inhibition of metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix protein that affects cell proliferation, cross-linking of extracellular collagen types, and establishment of the metastatic niche. There are 2 samples sent in triplicates.
2011-08-31 | E-GEOD-24249 | biostudies-arrayexpress