Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adipocytes disrupt the translational programme of Acute Lymphoblastic Leukaemia to favour tumour survival and persistence

ABSTRACT: Nalm-6 cells co-cultured with 3T3-L1 adipocytes or pre-adipocytes were subjected to quantitative LC-MS/MS phosphoproteomic analysis at two timepoints (+24h and +72h) to determine dynamics of cell signalling. Two independent biological replicates were analysed per condition.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell Line Cell, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Vinothini Rajeeve

LAB HEAD: Dr Pedro R Cutillas

PROVIDER: PXD019186 | Pride | 2021-06-09

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	F003984.mzid.gz	Mzid
	F003984.pride.mztab.gz	Mztab
	F003985.mzid.gz	Mzid
	F003985.pride.mztab.gz	Mztab
	F003986.mzid.gz	Mzid

Items per page:

1 - 5 of 80

Similar Datasets

BRAF mutations disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mouse and humans

Project description:Germline mutations in BRAF and other components of the Mitogen-Activated Protein Kinase (MAPK) pathway are associated with the congenital syndromes collectively known as RASopathies. Here, we report the association of Septo-Optic Dysplasia (SOD) including hypopituitarism and Cardio-Facio-Cutaneous (CFC) syndrome in patients harboring mutations in BRAF. Phosphoproteomic analyses demonstrate that these genetic variants are gain-of-function mutations leading to activation of the MAPK pathway. Activation of the MAPK pathway by conditional expression of the BrafV600E/+ allele, or the knock-in BrafQ241R/+ allele (corresponding to the most frequent human CFC-causing mutation, BRAFp.Q257R), leads to abnormal cell lineage determination and terminal differentiation of hormone-producing cells, causing hypopituitarism. Expression of the BrafV600E/+ allele in embryonic pituitary progenitors leads to an increased expression in cell cycle inhibitors, cell growth arrest and apoptosis but not tumour formation. Our findings show a critical role for BRAF in hypothalamo-pituitary-axis development both in mouse and human and implicate mutations found in RASopathies as a cause of endocrine deficiencies in humans

2020-11-17 | PXD018190 | Pride

Characterising early phosphorylation events upon HER2 protein overexpression

Project description:HER2 transduced cells which we will refer to as HER2-DOX –. These cells are 99% GFP positive (i.e., 99% cells have HER2 transduced, un-induced). As a control, we had GFP empty vector transduced MCF10A cells (95% have GFP transduced). Both cell types in triplicates. We had 4 time-points 0h, 30 mins, 4hours, and 7 hours (time duration for which HER2 will be induced). DOX was added to the GFP-MCF10A cells as a control. Only 1ug/ml of DOX was be used.

2023-01-23 | PXD034105 | Pride

Cell rearrangement during angiogenesis requires suppression of actomyosin at cell-cell contacts via PI3-kinase.

Project description:Sprouting angiogenesis is a highly dynamic process which relies on the continuous interchange of endothelial cell relative position within the vascular sprout, a process mediated by cell rearrangements. Here we take advantage of a previous identified role of p110a/PI3K regulating endothelial cell motility to address how cell rearrangement and interaction regulate vessel growth. By using advanced fluorescent zebrafish models and a tamoxifen-inducible endothelial-specific gene targeting in the postnatal mouse retina, we demonstrate that inactivation of the p110a isoform of PI3K in endothelial cells is a good model to study cell shuffling in the growing vasculature. We identify that a failure of endothelial cells to rearrange results in cell elongation and inability to stabilize new contacts upon anastomosis. Instead of rearrange, blockade of p110 signaling drive these cells to grow in a three dimension fashion by sending multiple protrusions which lack lumen and fail to stabilize upon anastomosis. Through a combination of in vivo and in vitro approaches together with a global phosphoproteomic screen, we discover that p110a signaling stimulates cell rearrangements by suppressing actomyosin contractility in a myosin light chain phosphatase (MLCP) dependent manner. Together, our findings highlight the importance of cell rearrangement orchestrating several steps within the angiogenic program and uncover a critical role of the p110a/MLCP axis to suppress actomyosin contractility.

2018-10-02 | PXD007060 | Pride

Signaling network diversification during differentiation sensitizes AML cells to PAK and MEK inhibitors

Project description:A main requirement for precision medicine is the identification of patients that are more likely to respond to a particular drug. AML is a heterogeneous disease in which molecules associated to kinase signaling are frequently mutated. However, no kinase inhibitor has been approved for the treatment of this malignancy. Thus, patient stratification requires new molecular profiling techniques in addition of to the current sequencing strategies. We have used a multiomics approach that combines proteomics, phosphoproteomics, mass cytometry and DNA sequencing to classify primary AML cells derived from 36 patients. Comprehensive integrative analysis identified molecular signatures based on phosphopeptide abundance or surface marker expression that separate AML cases according to their differentiation status. Differentiated cells presented a particular pattern of protein phosphorylation, an enrichment in the activity of several kinases and a higher sensitivity to PAK, MEK and PKC/FLT3 inhibitors. In addition, mutations in proteins closely linked to kinase signaling were more frequent on differentiated cells. Interestingly the set of patients with differentiated cells as clustered by marker expression signatures showed an increased overall survival in our set of patients and in the TCGA database registered cohort. Thus, molecular differentiation signatures could be used as prognosis and drug response markers in order to implement the application of precision medicine in AML patients.

2020-04-15 | PXD005978 | Pride

An increase in oxidative stress downstream of mTORC1 but not AKT causes a proliferative defect in cancer cells with acquired resistance to PI3K/mTOR inhibitors

Project description:Proteomics and phosphoproteomics analysis of MCF7 cells sensitive and resistant to the PI3K inhibitor GDC-0941. The analysis was done for parental and 3 resistant cell lines maintained in the presence or the absence of the drug. One of the resistant cell lines (G2) was also treated with vehicle or the kinase inhibitors GDC0941, MK-2206 and Ku-0063794 for 2h. The proteomics analysis of sensitive and resistant MCF7 cells in basal conditions and phosphoproteomics analysis of the G2 cells in the presence of inhibitors of the PI3K pathway were run in a nano flow ultrahigh pressure liquid chromatography (UPLC, nano Acquity, Waters) coupled to an LTQ-Orbitrap XL mass spectrometer (Thermo Fisher Scientific). The phosphoproteomics study of sensitive and resistant MCF7 cells in basal conditions was run in a Dionex UltiMate 3000 RSLCnano coupled to an Orbitrap Q Exactive Plus mass spectrometer (Thermo Fisher Scientific).

2018-04-09 | PXD003594 | Pride

Low endothelial cell FAK expression reduces pancreatic ductal adenocarcinoma liver metastasis after gemcitabine treatment

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a high level of liver metastasis. Despite substantial advances, resistance to therapy, including gemcitabine, is still a major obstacle to improved progression free survival. Recent studies have indicated that endothelial cell (EC) focal adhesion kinase (FAK) regulates DNA-damaging therapy induced angiocrine factors and chemosensitivity in malignant cells. However, the effect of EC-FAK regulated angiocrine signalling in chemosensitivity of metastatic PDAC remains unexplored. Here, we show that inducible loss of EC-FAK in both orthotopic and spontaneous mouse models of PDAC reduces liver metastasis and improves survival rates in gemcitabine treated, but not untreated, mice, without affecting primary tumour growth, tumour vascularization, blood vessel leakage or early metastatic events. Phosphoproteomics analysis show a downregulation of the MAPK/ RAF/ PAK signalling pathways in gemcitabine treated FAK-depleted ECs compared to gemcitabine treated WT ECs. Moreover, low levels of EC-FAK correlate with increased survival and reduced relapse in gemcitabine treated human PDAC patients, supporting the clinical relevance of our findings. Altogether, we have identified a new role of EC-FAK regulating PDAC liver metastasis upon gemcitabine treatment that impacts on survival.

2023-03-10 | PXD021542 | Pride

ECM-enriched proteomics of human fallopian tube, fimbria and ovarian tissue

Project description:We analysed the extracellular matrix (ECM) landscape of fresh, healthy tissues from human fallopian tube (FT), fimbria (FB, the tissue of origin of serous tubal intraepithelial lesions) and ovarian tissue (OV). The aim was to identify differentially expressed matrix proteins between FB and FT or OV which may promote the neoplastic transformation of serous tubal intraepithelial lesions (STICs) into high-grade serous ovarian cancer, HGSOC, and metastasis from the FB to the OV.

2022-06-20 | PXD023912 | Pride

Elucidating the role of the kinase activity of endothelial cell focal adhesion kinase in angiocrine signalling and tumour growth

Project description:A common limitation of cancer treatments is chemotherapy resistance. We have previously identified a molecular mechanism where chemotherapy resistance is regulated by endothelial cells. Endothelial cell specific knockout of focal adhesion kinase (FAK) sensitises tumour cells to DNA-damaging therapies, reducing tumour growth in mice. Our current study addresses the kinase dependent component of endothelial cell FAK sensitisation to the DNA damaging chemotherapeutic drug doxorubicin. FAK is recognised as a therapeutic target in tumour cells, leading to the development of a range of inhibitors, the majority being ATP competitive kinase inhibitors. We demonstrate that specific inactivation of the FAK kinase domain in endothelial cells of blood vessels in established subcutaneous B16F0 tumours sensitises melanoma cells to doxorubicin. Tumour growth was reduced in response to doxorubicin treatment in FAK kinase-dead but not in wild-type mice. Furthermore, we demonstrate that doxorubicin reduces perivascular proliferation, enhances apoptosis and DNA-damage in endothelial cell FAK kinase dead tumours. When we treated human pulmonary microvascular endothelial cells with the FAK kinase inhibitors defactinib, PF-562,271 and PF-573,228 in combination with doxorubicin, we observed a reduction in cytokine levels, implying a possible mechanism for FAK kinase domain in chemosensitisation. Together, these results confirm the role of the kinase domain of EC-FAK in chemosensitising tumour cells to doxorubicin.

2021-11-02 | PXD019728 | Pride

Expression data from mouse bone marrow adipocytes with age

Project description:The aim of this study was to characterize the age-related gene expression profiles between bone marrow adipocytes and peripheral white adipocytes. Alterations of gene expression with aging were analyzed in bone marrow and peripheral white adipocytes isolated from C57BL/6J male mice using Affymetrix Mouse Gene 1.0 ST arrays. Bone marrow adipocytes and peripheral white adipocytes (n=6-10 animals per group) were isolated from male C57BL/6J mice (6-months, 14-months and 18-months of age). Samples were grouped into cell type (bone marrow adipocytes vs. peripheral adipocytes) and age (6-month (6M), 14-month (14M) and 18-month (18M)).

2011-11-29 | E-GEOD-25905 | biostudies-arrayexpress

Long non-coding RNAs regulate adipogenesis (Illumina RNA-Seq)

Project description:Adipogenesis involves the regulation of hundreds of genes by several well-studied proteins, but the role of long, noncoding RNAs in this process has not been defined. We track the regulation of hundreds of lncRNAs during adipocyte differentiation, and find several that are essential for this process. We extractedbrown and white primary adipocytes and pre-adipocytes and profiled lncRNA expresssion via mRNA-Seq. We also profiled cultured, differentiated adipocytes to verify that we could recapitulate the adipocyte expression profile in preparation for a loss-of-function screen for essential adipogenic lincRNAs.

2013-02-15 | E-GEOD-29898 | biostudies-arrayexpress

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