Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumor-produced and aging-associated oncometabolite, methylmalonic acid, promotes cancer-associated fibroblast activation to drive metastatic progression

ABSTRACT: Tumor-produced and aging-associated oncometabolite, methylmalonic acid, promotes cancer-associated fibroblast activation to drive metastatic progression

PROVIDER: PRJNA788944 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR17230995_1.fastq.gz	Fastqsanger.gz
	SRR17230995_2.fastq.gz	Fastqsanger.gz
	SRR17230996_1.fastq.gz	Fastqsanger.gz
	SRR17230996_2.fastq.gz	Fastqsanger.gz
	SRR17230997_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Tumor-produced and aging-associated oncometabolite, methylmalonic acid, promotes cancer-associated fibroblast activation to drive metastatic progression

Project description:The systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) that fosters cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite that is also produced by aggressive cancer cells, activates fibroblasts in the TME and stimulates the release of extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways in CAFs. EV-associated IL-6 functions as a stroma-tumor messenger that activates the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promote an epithelial-to-mesenchymal transition (EMT) and drug resistance in vitro, and metastatic progression in vivo. Our findings reveal the role of MMA in the activation of CAFs to drive metastatic reprogramming, unveiling multiple potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.

2022-10-04 | GSE190929 | GEO

Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression

Project description:A quantitative comparison of extracellular vesicle proteins in cultured human fibroblasts treated with methylmalonic acid.

| MSV000090312 | MassIVE

Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression.

Project description:The systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) fostering cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite also produced by aggressive cancer cells, activates fibroblasts in the TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways. EV-associated IL-6 functions as a stroma-tumor messenger, activating the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promoting pro-aggressive behaviors. Our findings define the role of MMA in CAF activation to drive metastatic reprogramming, unveiling potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.

| S-EPMC9584945 | biostudies-literature

Pancreatic adenocarcinoma associated fibroblast cells

Project description:Pancreatic adenocarcinoma associated fibroblast cells

| PRJNA318744 | ENA

Suppression of antitumor immunity by the oncometabolite 2-hydroxyglutarate

Project description:Isocitrate dehydrogenase (IDH) mutations, a hallmark of gliomagenesis, result in the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG) which is thought to promote tumorigenesis via DNA methylation. Here we identify an additional immunosuppressive activity of R-2-HG: Tumor cell-derived R-2-HG is taken up by T-cells where it induces a strong and immediate perturbation of calcium- and ATP-dependent signaling events, and polyamine biosynthesis. This results in a profound suppression of antigen-specific T-cell activation and effector cytokine production in experimental mouse and human systems. In a large cohort of WHO grade II and III gliomas, IDH1 mutant tumors display reduced infiltration by T-cells compared to IDH1 wildtype tumors. Spontaneous and induced mutation-specific antitumor immunity to syngeneic IDH1-mutant tumors in MHC-humanized mice is improved by isolated genetic ablation of the neomorphic enzymatic function of mutant IDH1. Taken together, these data attribute a novel, fundamentally non-tumor-cell-autonomous role of an oncometabolite in shaping the tumor immune microenvironment. We investigated the effects of exogenous R-2-HG on primary human T cells.

2016-07-27 | E-GEOD-84849 | biostudies-arrayexpress

Proteomic analysis of methylmalonic acidemia fibroblasts

Project description:Methylmalonic academia (MMA) is a rare inborn error of the metabolism due to defects of the methylmalonyl-CoA mutase (MUT) enzyme that result in methylmalonic acid accumulation in the blood and increased excretion in urine. Affected patients can manifest vomiting, dehydration, hypotonia, developmental delay and failure to thrive. The emergency treatment of the newborns with MMA mainly comprises rehydration and promotion of anabolism, followed by long-term dietary management that mostly includes restriction of propiogenic amino acids by a low protein diet and carnitine and vitamin B12 supplementation. The effects of MUT deficiency on the cellular damage in patients is still unknown. Fibroblasts obtained from two distinct MMA patients were analyzed by shotgun label-free quantitative (LFQ) proteomics.

2024-06-14 | PXD044025 | Pride

Whole transcriptome analysis of cancer-associated fibroblast

Project description:Whole transcriptome analysis of cancer-associated fibroblast

| PRJNA847900 | ENA

Gene Expression Analysis of Cancer-Associated Fibroblast (CAF) compared to Normal Fibroblast (NF)

Project description:Gene Expression Analysis of Cancer-Associated Fibroblast (CAF) compared to Normal Fibroblast (NF)

| PRJNA241179 | ENA

A compositional change in exomiRs during normal fibroblast to cancer-associated fibroblast transition.

Project description:A compositional change in exomiRs during normal fibroblast to cancer-associated fibroblast transition.

| PRJNA553539 | ENA

Methylmalonic acidemia triggers lysosomal-autophagy dysfunctions

Project description:Methylmalonic acidemia (MMA) is a rare inborn error of propionate metabolism caused by deficiency of the mitochondrial methylmalonyl-CoA mutase (MUT) enzyme. As matter of fact, MMA patients manifest impairment of the primary metabolic network with profound damages that involve several cell components, many of which have not been discovered yet. We employed cellular models and patients-derived fibroblasts to refine and uncover new pathologic mechanisms connected with MUT deficiency through the combination of multi-proteomics and bioinformatics approaches.

2024-05-23 | PXD044101 | Pride

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