Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA283830 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGFβ-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men. KC (Atm+/+) and AKC (Atm-/-) mouse pancreata at 5 weeks old (n= 3 KC; n= 3 AKC) or 10 weeks old (n=3 KC; n=4 AKC) were subjected to microarray analysis.
2015-08-07 | E-GEOD-68808 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGFβ-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men.
2015-08-07 | GSE68808 | GEO
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
Project description:Gene expression in epithelial, EMT (epithelial-mesenchymal transition) and MET (mesenchymal-epithelial transition) cells
| PRJNA209196 | ENA
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
Project description:Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities and ultimately metastasis. We have employed a lineage traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that have undergone P-EMT and complete EMT (C-EMT). Using an unbiased quantitative proteomics approach, we found that the morphology of the organoids could predict EMT state, with solid organoids associated with a C-EMT signature. We also observed that exogenous TGFb1 could induce a solid organoid morphology that was associated with changes in the S100 family of proteins and the formation of high-grade tumors. Our work reveals that S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome.
2023-02-24 | PXD030992 | Pride
Project description:Oncogenic transformation alters the metabolism of cellular lipids to sustain tumor growth. We define a reciprocal mechanism by which cholesterol metabolism controls the formation and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of Nsdhl, or treatment with cholesterol-lowering statins caused murine pancreatic carcinomas induced by KrasG12D expression and homozygous Trp53 loss to undergo a differentiation switch from a glandular to basal (mesenchymal) phenotype. In parallel, PDACs from patients receiving statins had enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induced sterol response element binding protein 1 (SREBP1), promoting autocrine transforming growth factor beta (TGF) signaling, inducing epithelial-mesenchymal transition. Activation of promesenchymal TGFβ effectors by cholesterol-lowering statins may select for poorly differentiated carcinomas.
2020-08-14 | GSE156210 | GEO
Project description:Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of PFKP (phosphofructokinase, platelet), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of PFKP (phosphofructokinase, platelet), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.
2017-11-07 | MTBLS387 | MetaboLights
Project description:Tumor Associated Calcium Signal Transducer 2 (TACSTD2) is one of the cancer-related genes whose overexpression correlates with tumor progression and invasiveness in human colorectal cancer. TACSTD2 gene encodes for a transmembrane glycoprotein TROP2, which is implicated in altered expression of epithelial-mesenchymal transition (EMT) markers and may play a role in metastasis formation. To monitor the onset of TROP2 in hyperplastic cells and its effect on aberrant signaling potentially leading to tumor growth, we isolated epithelial cells from the mouse small intestine 7 days after disruption of the Adenomatous polyposis coli (Apc) gene. Loss of APC tumor suppressor function is the most common initial step in the development of colon cancer in humans. In the mice, the epithelial hyperproliferation occurs within a few days after Apc disruption, accompanied by the formation of ectopic crypts, followed by the formation of microadenomas over time. We performed expression profiling of Trop2+ and Trop2- hyperproliferating cells and, in addition, non-proliferating cells of the intestinal epithelium, including predominantly differentiated cells.
2022-11-29 | E-MTAB-11377 | biostudies-arrayexpress
Project description:Loss of JNK in Breast Epithelium Accelerates Tumor Formation
| PRJNA358050 | ENA