Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SAMD1 suppresses epithelial-mesenchymal transition pathways in pancreatic ductal adenocarcinoma [RNA-Seq]

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with epithelial-mesenchymal transition (EMT). Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239414 | GEO | 2024/06/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SAMD1 suppresses epithelial-mesenchymal transition pathways in pancreatic ductal adenocarcinoma [ChIP-Seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with epithelial-mesenchymal transition (EMT). Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.

2024-06-27 | GSE239415 | GEO

SAMD1 suppresses epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma.

Project description:SAMD1, a CpG island-binding protein, plays a pivotal role in the repression of its target genes by influencing the activity of KDM1A. Despite its significant correlation with outcomes in various tumor types, SAMD1's role in cancer has remained largely unexplored. In this study, we focus on pancreatic ductal adenocarcinoma (PDAC) and reveal that SAMD1 is a repressor of genes associated with epithelial-mesenchymal transition (EMT). Upon depletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. Furthermore, high SAMD1 expression in PDAC patients correlated with lower expression of EMT signature genes and better prognosis, further underscoring its suppressive role. In-depth analysis revealed that SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-Cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Our investigations further demonstrated reduced chromatin-binding activity of SAMD1 in PDAC cells, prompting a search for regulatory mechanisms. This led to the discovery of the FBXO11-containing E3 ubiquitin ligase complex as a novel interactor of SAMD1, critically influencing its chromatin binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, implying an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide new insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this particular cancer type.

2024-07-12 | PXD044104 | Pride

EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer

Project description:<p>The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC.</p>

2021-10-15 | MTBLS1925 | MetaboLights

Proteomic analysis of breast EMT cell models reveal UGDH is upregulated during EMT and holds the potential as a clinical target

Project description:Epithelial–mesenchymal transition (EMT) is known to be involved in cancer metastasis and pathogenesis. Metabolic re-wiring is now considered to be one of the hallmarks of cancer. In this study, we studied the metabolic changes during EMT in three breast EMT cell models with a proteomic approach. The study showed well-known changes during EMT including CDH1, CDH2, VIM, LGALS1, SERPINE1 and PKP3. It also suggested a list of dysregulated metabolic enzymes: SORD, TSTA3, FDFT1 and UGDH. UGDH had the biggest change and is associated with patient survival. We further studied the role of UGDH in EMT and found out knockdown of UGDH with siRNA can decrease the intracellular glycerophosphocholine level and it can also slow cell proliferation and invasion in mesenchymal cells. Besides, knockdown of UGDH downregulated the expression of a well-known EMT marker, SNAI1. PDGFRB is highly expressed in mesenchymal cells and PDGFD is highly secreted from mesenchymal cells. Knockdown of PDGFRB with siRNA downregulated UGDH potentially via NFkB.

2022-01-04 | PXD024164 | Pride

WDR5 regulates EMT and metastasis in breast cancer by activating TGFB pathway [RNA-seq PDX]

Project description:The core subunit of the COMPASS-like complex, WD Repeat Domain 5 (WDR5) has a prominent role in reprogramming and Epithelial-to-Mesenchymal transition (EMT) in different tumor types. Our evidences support a model in which WDR5 is prominent for EMT and metastasis dissemination in breast cancer patient-derived xenografts and cell lines. Moreover, WDR5 silencing abrogates TGFB pathway activation and reverts mesenchymal into epithelial phenotype, by inhibiting transcription of main master regulators of EMT (CDH2, TWIST1, SNAI1, SNAI2 and ZEB1). Our data suggest that WDR5 inhibition may be a successful approach to prevent progression of metastatic BC.

2019-12-17 | GSE113288 | GEO

WDR5 regulates EMT and metastasis in breast cancer by activating TGFB pathway [RNA-seq CCL]

2019-12-17 | GSE113283 | GEO

WDR5 regulates EMT and metastasis in breast cancer by activating TGFB pathway [ChIP-seq]

2019-12-17 | GSE113279 | GEO

Disturbed Balance of Protein Phosphatase Type 2A (PP2A) is Driving Epithelial-to-Mesenchymal Transition in Human Pan-creatic Cancer Patients

Project description:The incidence for pancreatic ductal adenocarcinoma (PDAC) is rising which has a low survival rate. In cancer, Epithelial-to-Mesenchymal transition (EMT) contribute to an aggressive phenotype. Protein Phosphatase Type 2A (PP2A) are initially regarded as tumor suppressors, the connection with EMT in patients is uncertain. We investigated the relation of a ‘PP2A’ gene signature (en-compassing catalytic, structural and regulatory subunits; and endogenous PP2A inhibitors and activators) with EMT in PDAC patients. We could demonstrate a link between PDAC and EMT in four patient datasets using datamining, correlation study and gene set analysis. Furthermore, we identified a strong association of PP2A with EMT in advanced pancreatic cancer patients and in particular a significant upregulation of PP2A inhibitor genes in aggressive/EMT-high PDAC. In vitro, pharmacological inhibition of PP2A through Okadaic acid induced EMT in human pancreatic cells. Two different cell models were developed and their morphology, gene and protein expression determined. In the more advanced OA-induced EMT model (OA7G), statistical changes in proteins of natural PP2A-inhibitors was observed and this requires further investigations. Translationally, these observations indicate that PP2A could be a central factor in cancer and it is therefore attractive to test compounds that can target PP2A enzyme activity in PDAC.

2023-07-20 | PXD037976 | Pride

Selvaggio2020 - Microenvironment control of hybrid Epithelial-Mesenchymal phenotypes

Project description:Epithelial to Mesenchymal Transition (EMT) has been associated with cancer cell heterogeneity, plasticity and metastasis. It has been the subject of several modeling effort. This logical model of the EMT cellular network aims to assess microenvironmental signals controlling cancer-associated phenotypes amid the EMT continuum. Its outcomes relate to the qualitative degrees of cell adhesions by adherent junctions and focal adhesions, two features affected during EMT. Model attractors recover epithelial, mesenchymal and hybrid phenotypes, and simulations show that hybrid phenotypes may arise through independent molecular paths, involving stringent extrinsic signals. Of particular interest, model predictions and their experimental validations indicated that: 1) ECM stiffening is a prerequisite for cells overactivating FAK-SRC to upregulate SNAIL1 and acquire a mesenchymal phenotype, and 2) FAK-SRC inhibition of cell-cell contacts through the Receptor Protein Tyrosine Phosphates kappa leads to the acquisition of a full mesenchymal rather than a hybrid phenotype.

2020-06-30 | MODEL2004040001 | BioModels

"High Levels of EMT-TFs for the Diagnosis of Colorectal Cancer (CRC)"

Project description:The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of colorectal cancer (CRC) patients and healthy controls, to determine the presence of disease, its progression and risk of recurrence.

| 2334276 | ecrin-mdr-crc

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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