Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vicious circle of LSD1 and TGF β1 promotes EMT of gastric cancer

ABSTRACT: Vicious circle of some key proteins is critical in the process of tumor development. Nevertheless, the mechanism of how the epigenetic modifiers are involved in was seldom reported and has not been clearly illustrated. We found the expression of lysine specific demethylase 1 (LSD1), the first identified histone lysine demethylase, is positively correlated with transforming growth factor beta 1 (TGF β1) in gastric cancer tissues and can be promoted by TGF β1 activated (p-EKR)-(NF-κB)-p300 signaling pathway, which resulted in the progression of epithelial-mesenchymal transition (EMT) in human gastric cancer cells. On the other hand, abrogation of LSD1 leads to the down regulation of TGF β1 as well as the EMT. But in benign cells, this circle was blocked by TGF β1 induced inactivation of ERK, which suggested the distinct roles of TGF β1 against LSD1 in gastric cancer cells and benign cells. This vicious cycle may illustrate a novel mechanism for EMT in gastric cancer mediate by TGF β1 and LSD1 but not in benign cells and may serve as a new strategy for the prevention of EMT for gastric cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84487 | GEO | 2016/07/19

SECONDARY ACCESSION(S): PRJNA329586

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Vicious circle of LSD1 and TGF Î²1 promotes EMT of gastric cancer

Project description:Vicious circle of some key proteins is critical in the process of tumor development. Nevertheless, the mechanism of how the epigenetic modifiers are involved in was seldom reported and has not been clearly illustrated. We found the expression of lysine specific demethylase 1 (LSD1), the first identified histone lysine demethylase, is positively correlated with transforming growth factor beta 1 (TGF Î²1) in gastric cancer tissues and can be promoted by TGF Î²1 activated (p-EKR)-(NF-ÎºB)-p300 signaling pathway, which resulted in the progression of epithelial-mesenchymal transition (EMT) in human gastric cancer cells. On the other hand, abrogation of LSD1 leads to the down regulation of TGF Î²1 as well as the EMT. But in benign cells, this circle was blocked by TGF Î²1 induced inactivation of ERK, which suggested the distinct roles of TGF Î²1 against LSD1 in gastric cancer cells and benign cells. This vicious cycle may illustrate a novel mechanism for EMT in gastric cancer mediate by TGF Î²1 and LSD1 but not in benign cells and may serve as a new strategy for the prevention of EMT for gastric cancer. Nuclear extracts prepared from MGC803 cells stably expressing Lenti-CAS9-sgRNA-puro for LSD1 or empty vector were used in immunoprecipitation reactions with antibodies against H3K4me2 and H3K9me2. Sequencing libraries were prepared using the TruSeq DNA Sample Prep Kit (Illumina) and sequencing was performed on a HiSeq2000 (Illumina).

2016-07-19 | E-GEOD-84487 | biostudies-arrayexpress

Homo sapiens

Project description:Vicious circle of LSD1 and TGF β1 promotes EMT of gastric cancer

| PRJNA329586 | ENA

Homo sapiens

Project description:A paracrine amplification loop between LSD1 and TGF β1 promotes EMT of gastric cancer

| PRJNA391553 | ENA

Small extracellular vesicles-delivered LSD1 promotes gastric cancer cell stemness

Project description:Although there are plenty of researches about nucleic acid in small extracellular vesicles (sEVs), properties of proteins identified as sEVs’ cargos and the mechanism of their action in recipient cell are poorly understood. Here, we show that lysine specific demethylase 1 (LSD1), the first identified histone demethylase in 2004, existed in the cell cultured medium of gastric cancer cells. Further investigation confirmed the presence of LSD1 in sEVs from gastric cancer cells and gastric cancer patient plasma, which is the first identified histone demethylase in sEVs. By shuttling from donor cells to recipient gastric cancer cells, sEVs-delivered LSD1 promoted the cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2 and CD44, and suppressed the oxaliplatin response of the recipient cells in vitro and in vivo, while LSD1 depleted sEVs failed to suppress the oxaliplatin response. Collectively, our findings give an evidence for LSD1 as a sEVs protein to promote stemness and suppress oxaliplatin response for the first time and constitute a future avenue to predict oxaliplatin response in gastric cancer clinically.

2021-07-30 | PXD021511 | Pride

Small extracellular vesicles-delivered LSD1 promotes gastric cancer cell stemness

2021-12-22 | PXD020223 | Pride

LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer

Project description:Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.

2018-01-11 | GSE104754 | GEO

The role of LSD1 in Epithelial to Mesenchymal Transition

2018-01-11 | GSE104753 | GEO

miR-134/487b/655 Cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to Gefitinib by targeting MAGI2 in lung adenocarcinoma cells.

Project description:Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA) -related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) in NSCLC. MiRNA expression profiles were examined before and after transforming growth factor-beta1 (TGF-β1) exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. MiRNA array and quantitative RT-PCR revealed that TGF-β1 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcinoma cells with EMT. MAGI2 (membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2), a predicted target of these miRNAs and a scaffold protein required for PTEN (phosphatase and tensin homolog), was diminished in A549 cells with EMT after the TGF-β1 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-β1-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-β1-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, whose suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be new therapeutic targets in advanced lung adenocarcinoma patients, depending on the EMT phenomenon.

2013-10-30 | GSE51828 | GEO

Overexpression of PHF8 promotes an EMT-related gene signature in MCF10A cells

Project description:PHF8 exerts distinct functions in different types of cancer. However, the mechanisms underlying its specific functions in each case remain obscure. To establish whether overexpression of PHF8 regulates the TGF-β induced the epithelial-mesenchymal transition (EMT), we treated MCF10A-Mock (control) and MCF10A-PHF8wt (overexpressing wild-type PHF8) cells with TGF-β1 for 0, 24, 48 and 72 hours and performed RNA-seq in biological duplicates. Our data indicated that EMT gene signatures were significantly enriched in MCF10A-PHF8 cells with TGF-β1 treatment at all time points, strongly indicating that PHF8 overexpression induces a sustained EMT signaling program.

2016-10-26 | GSE74377 | GEO

SOX11 promotes skin fibrosis by inducing fibrotic factors

Project description:In this study, we demonstrated that baseline SOX11 expression was significantly higher in dermal fibroblasts (DFs) isolated from patients with SSc than that in controls, and increased in response to TGF-b. We then showed that SOX11 is involved in the expression of periostin and some periostin-dependent fibrotic factors identified in lung fibroblasts previously. Moreover, we identified some fibrotic factors induced by SOX11 in DNA microarrays combining TGF-b induction and SOX11 knockdown. Finally, we showed that genetic deletion of SOX11 in Postn positive fibroblast cells protects from bleomycin (BLM)-induced skin fibrosis. Altogether, our data indicate that SOX11 and periostin forms a vicious circle and that TGF-b activates this circle specifically in SSc dermal fibroblasts.

2023-01-29 | GSE206473 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data