Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SILAC proteomics of cancer-associated fibroblasts (CAFs) and cancer cells

ABSTRACT: To study bi-directional signaling between cancer-associated fibroblasts (CAFs) and cancer cells, we used stable isotope labeling by amino acids in cell culture (SILAC) to determine changes in tyrosine phosphorylation upon direct contact of the two cell types.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryo, Fibroblast

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Arthur Salomon

LAB HEAD: Arthur Salomon

PROVIDER: PXD003574 | Pride | 2020-05-26

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis.

Curtis Marion M Kenny Hilary A HA Ashcroft Bradley B Mukherjee Abir A Johnson Alyssa A Zhang Yilin Y Helou Ynes Y Batlle Raquel R Liu Xiaojing X Gutierrez Nuria N Gao Xia X Yamada S Diane SD Lastra Ricardo R Montag Anthony A Ahsan Nagib N Locasale Jason W JW Salomon Arthur R AR Nebreda Angel R AR Lengyel Ernst E

Cell metabolism 20180830 1

Successful metastasis requires the co-evolution of stromal and cancer cells. We used stable isotope labeling of amino acids in cell culture coupled with quantitative, label-free phosphoproteomics to study the bidirectional signaling in ovarian cancer cells and human-derived, cancer-associated fibroblasts (CAFs) after co-culture. In cancer cells, the interaction with CAFs supported glycogenolysis under normoxic conditions and induced phosphorylation and activation of phosphoglucomutase 1, an enzy ...[more]

PMID: 30174305

Similar Datasets

Analysis of HeLa cells after transfection with miR-1, miR-124 and miR-181.

Project description:Analysis of HeLa cells at 24 hours after transfection with wild type miR-1, miR-124, miR-181 versus control transfected HeLa cells. Results were compared to protein down-regulation at 48 hours measured by SILAC-MS. Analysis of HeLa cells at 24 hours after transfection with wild type miR-1, miR-124, miR-181 versus control transfected HeLa cells. Results were compared to protein down-regulation at 48 hours measured by SILAC-MS.

2010-05-25 | E-GEOD-11968 | biostudies-arrayexpress

Carcinoma-associated fibroblasts stimulate cancer cell invasion by mechanically remodeling the basement membrane

Project description:The first step in metastasis is dissemination of tumor cells into the surrounding tissue, or stroma. In carcinomas, cancers of epithelial origin, tumor cells must first breach the basement membrane (BM), a network that encapsulates the tumor. As tumor progresses, other cell types that reside in the stroma, such as carcinoma-associated fibroblasts (CAFs) accumulate around the tumor. Whether CAFs can help cancer cells to breach the BM remains an open question. Here we show that CAFs promote cancer cell invasion by physically remodeling the BM. Using a novel 3D in vitro model we observed that primary CAFs isolated from colon cancer patients stimulate cancer cell invasion through a native mesenteric BM. This stimulated invasion is the result of the physical presence of CAFs rather than an increased invasive potential of cancer cells. In the presence of CAFs, cancer cells can invade the BM in a matrix metalloproteinase-independent manner. Using live imaging, we found that CAFs actively pull and stretch the BM, leading to the formation of gaps through which cancer cells can migrate. Notably, CAF-mediated gap-widening is independent of proteolysis but relies on actomyosin contractility. We propose that CAFs exert mechanical forces that alter the organization and the physical properties of the BM, making it permissive for cancer cell invasion.

2017-09-18 | PXD003670 | Pride

SILAC proteomics analysis to discover effect sensors of EGFR inhibition

Project description:Targeted therapies against EGFR show clinical benefit, but resistance to these agents invariably develops. Thus, there is a need for dynamic biomarkers - effect sensors - that reflect treatment with EGFR therapeutics during therapy. Making use of SILAC-labeling we aimed to discover plasma membrane proteins that become differentially expressed after treatment with EGFR inhibitor erlotinib in three erlotinib-sensitive breast cancer cell lines.

2018-10-18 | PXD005985 | Pride

Ovarian Cancer Lipid raft proteomics and role of OPCML

Project description:ipid rafts are dynamic membrane micro-domains that orchestrate molecular interactions and are implicated in cancer development. To understand potential role of tumor suppressor OPCML on the altered dynamics of lipid raft residing proteins, we performed quantitative (SILAC) proteomics experiment. We recently found that OPCML negatively regulates a subset of receptor tyrosine kinases (RTKs) by altering their recycling and ubiquitin-mediated degradation via sequestration to lipid rafts; however, the molecular mechanism linking OPCML tumor suppressor expression to altered RTK trafficking remains unclear. Here we performed a quantitative lipid raft proteomics study to dissect raft-mediated mechanism of OPCML-regulated tumor suppression. We also examined raft-associated mechanism of OPCML P95R, a common mutation resulting in substitution of proline to arginine at position 95, mediated regulation of adhesion potential of tumors.

2017-03-16 | PXD006078 | Pride

Tumor matrix stiffness induces CCN1/CYR61 upregulation of N-Cadherin to promote cancer cell trans-endothelial migration and metastasis

Project description:Tumor progression is often accompanied with increased extracellular matrix stiffness, but how this affects endothelial cells (ECs) is largely unknown. We used mass spectrometry to analyse the proteomic changes of primary human ECs cultured on physiological or tumor stiffness and found that CCN1/CYR61 is highly induced by tumor stiffness. Knock out of Ccn1 in the vasculature of Ccn1loxP/loxP mice by administrating a soluble form of Cre shows that fewer of the treated mice harbour circulating tumor cells and lung metastases, without affecting primary tumor growth, using the B16F10 syngeneic mouse melanoma model This demonstrates that CCN1 loss in the host impairs cancer metastasis and we dissected the molecular mechanism in vitro. Stiffness-induced CCN1 acts via (integrin αvβ3), FAK, beta-catenin signalling to increase N-Cadherin expression in ECs, which, in turn, leads to an elevated adhesion of cancer cells to ECs via N-Cadherin homophilic interactions.

2017-07-07 | PXD003316 | Pride

Proteomic analysis of ∆4-CYB complex III mutant cybrids

Project description:The mitochondrial respiratory chain (MRC) enzymes associate in supercomplexes (SC). This structural interdependency may explain why defects in a single component often produce combined enzyme deficiencies in patients. A point in case is the alleged destabilization of complex I in the absence of complex III. To clarify the structural and functional relationships between complexes, we have used comprehensive proteomic, functional and biogenetical approaches to analyze a MT-CYB-deficient human cell line.

2020-01-07 | PXD016521 | Pride

Ferlins and TgDOC2 in Toxoplasma microneme, rhoptry and dense granule secretion

Project description:Stable Isotope Labeling with Amino acids in Cell culture (SILAC) proteomics on the proteinsreleased in a set of T. gondii secretion mutants.

2021-09-10 | PXD024210 | Pride

A PTPB1-Cdk3 signaling axis promotes cell cycle progression of human glioblastoma cells through an Rb-E2F dependent pathway

Project description:Protein tyrosine phosphatase 1B (PTP1B) plays a key role in developing different types of cancer. However, the molecular mechanism underlying this effect is unclear. To identify possible molecular targets of PTP1B that mediate its positive role in tumorigenesis, we undertook a SILAC-based phosphoproteomic approach, which allowed us to identify the Cyclin-dependent kinase 3 (Cdk3) as a novel PTP1B substrate. Molecular docking studies revealed stable interactions between the PTP1B catalytic domain and Cdk3. In addition, we observed that PTP1B dephosphorylates Cdk3 at Tyrosine residue 15 in vitro and interacts with it in the nucleus and cytoplasm of human glioblastoma (GB) cells. Finally, we found that the pharmacological inhibition of PTP1B or its depletion with siRNA leads to cell cycle arrest with the diminished activity of Cdk3, the consequent hypophosphorylation of Rb, and the down-regulation of E2F and its target genes Cdk1, Cyclin A, and Cyclin E1. These data delineate a novel signaling pathway from PTP1B to Cdk3 required for efficient cell cycle progression in an Rb-E2F dependent manner in human GB cells and suggest new therapeutic strategies for treating these tumors.

2023-12-05 | PXD046000 | Pride

Identification of potential substrates of TRABID in HeLa cells using SILAC

Project description:Immune checkpoint blockades (ICBs) have been approved for treating multiple cancer types, but the response rate is limited for many solid tumors. Much efforts have been devoted to understand the mechanisms governing ICB therapy efficacy and the abundance of tumor-infiltrating lymphocytes is among the factors that influence on ICB responsiveness. The deubiquitinase TRABID was identified in our previous study as a positive regulator of autophagy by stabilizing VPS34, the class III PI3K critical for autophagosome formation. In this study, we identify an upregulation of TRABID in mitosis and its critical role in mitotic progression through deubiquitination and stabilization of AURKB and BIRC5, two subunits of the chromosome passenger complex governing multiple mitotic steps. Furthermore, TRABID depletion induces micronuclei phenotype, which is likely mediated by the combinatory defects in mitosis and autophagy. Consequently, TRABID depletion or inhibition activates cGAS/STING pathway to induce type I interferon production and inflammatory responses. TRABID depletion in tumors cells reduces tumor burden and promotes anti-tumor immune surveillance by increasing tumor infiltration of CD4+ and CD8+ T cells and NK cells and reducing Treg cells. Clinically, TRABID expression in multiple cancer types correlates negatively with the infiltration of anti-tumor immune cells and positively with that of pro-tumor immune cells. Our study supports a suppressive role of tumor-intrinsic TRABID in anti-tumor immunity and suggests TRABID inhibitor as a promising agent for enhancing the sensitivity of solid tumors to ICB therapy.

2023-05-11 | PXD035002 | Pride

Identification of RNA binding proteins that interact with AU-rich elements of Lif 3`UTR

Project description:Leukemia inhibitory factor (LIF) is an important endogenous factor for photoreceptor protection. Lif is known to be upregulated both in induced and inherited disease models of photoreceptor degeneration only in a subset of Muller cells. Since Lif is induced in Muller cells in response to photoreceptor injury, we studied its regulation in Muller cells. We have recently identified several AU-rich elements (AREs) within the 3′ untranslated region (UTR) of Lif . We also showed that as a result of these elements Lif encodes a highly unstable mRNA. mRNAs containing AREs in the 3`UTR undergo rapid ARE-mediated mRNA decay in the cytoplasm which is mediated by the RNA–binding proteins. In order to identify the RNA-binding proteins that are involved in the regulation of Lif transcripts, we will use the biotin-labelled RNA. By using this methodology, we will isolate the related RNA binding proteins. We plan to analyze the isolated proteins by mass spectrometry, and compare the mass spectrometry results of different regions with or without AREs . Once we identify the specific proteins that bind only to AREs, we will do the functional characterization of these proteins by cotransfecting the constructs with AREs and the siRNA that inhibits the expression of related RNA binding protein.

2016-07-20 | PXD001463 | Pride

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