Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of Metabolism by LSR (part II)

ABSTRACT: Our aim is to identify the LSR-driven metabolomics profile of breast cancer cells in lean and obesogenic environments. Breast cancer cell models with high or undetectable levels of LSR, including drug resistance models, were cultured in lean and obesogenic environments and comprehensive metabolomics profiling, including lipidomics-focused sub-analyses were performed. The metabolomics analyses using both approaches will help us determine if LSR enhances aggressive breast cancer phenotypes via modulation of cellular bioenergetic metabolism, ultimately contributing to poor patient outcome.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Cells

DISEASE(S): Cancer

SUBMITTER: Susan Sumner

PROVIDER: ST000529 | MetabolomicsWorkbench | Fri Dec 30 00:00:00 GMT 2016

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Regulation of Metabolism by LSR

Project description:Our aim is to identify the LSR-driven metabolomics profile of breast cancer cells in lean and obesogenic environments. Breast cancer cell models with high or undetectable levels of LSR, including drug resistance models, were cultured in lean and obesogenic environments and comprehensive metabolomics profiling, including lipidomics-focused sub-analyses were performed. The metabolomics analyses using both approaches will help us determine if LSR enhances aggressive breast cancer phenotypes via modulation of cellular bioenergetic metabolism, ultimately contributing to poor patient outcome.

2016-12-29 | ST000528 | MetabolomicsWorkbench

Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer [tumor]

Project description:Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that a majority of patients fail to respond, which is partly attributable to immunosuppression. Obesity appears to improve immune checkpoint therapies in some cancers but impacts on breast cancer (BC) remain unknown. In obese mice fed an obesogenic or lean controls on a low fat diet, mice are injected with BC cells andtreated with anti-PD-1 or control. Obesity leads to immunosuppression systemically in tumor-free mice that is exacerbated in tumor-bearing mice. Obesity augments tumor incidence and progression. Anti-PD-1 induces regression in lean mice and potently abrogates progression in obese mice. Anti PD-1 significantly reduces immunosuppressive cells and elevates anti-tumor immune cells. Lamb2, downregulated by anti-PD1, significantly predict patient survival. Last, we identify a microbial signature associated with anti-PD-1 efficacy. In sum, anti-PD-1 is highly efficacious in obese mice by reinvigorating durable antitumor immunity.

2021-05-08 | GSE174053 | GEO

Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer [Mammary fat pad, MFP]

2021-05-08 | GSE174044 | GEO

Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet

Project description:Foxp3+CD4+ regulatory T (Treg) cells found within tissues regulate local immunity, inflammation and homeostasis. Tregs in epididymal visceral adipose tissue (eVAT) are critical regulators of local and systemic inflammation and metabolism. During aging and under obesogenic conditions, eVAT Tregs undergo transcriptional and phenotypic changes and are important for containing inflammation and normalizing metabolic indices. We have employed single-cell RNA sequencing, single-cell Tra and Trb sequencing, adoptive transfers, photoconvertible mice, cellular interaction analyses and in vitro cultures to dissect the evolving heterogeneity of eVAT Tregs with aging and obesity. Distinct Treg subtypes with distinguishable gene-expression profiles and functional roles were enriched at differing ages and with differing diets. Like those in lean mice, eVAT Tregs in obese mice were not primarily recruited from the circulation but instead underwent local expansion and had a distinct and diversified T cell receptor repertoire. The different eVAT-Treg subtypes specialized in different functions; for example, the subtypes enriched in lean, but not obese, mice suppressed adipogenesis. The existence of functionally divergent eVAT-Treg subtypes in response to obesogenic conditions presents possibilities for precision therapeutics in the context of obesity.

2024-02-05 | GSE248440 | GEO

FDXR Drives Primary and Endocrine Resistant Tumor Cell Growth in ER+ Breast Cancer via CPT1A-Mediated Fatty Acid Oxidation

Project description:The majority of breast cancers (BCs) harboring estrogen receptor (ER) have shown endocrine resistance. Our previous study has demonstrated that ferredoxin reductase (FDXR) promotes mitochondrial function and ER+ breast tumorigenesis. Here, integrative analyses of targeted metabolomics assay and gene expression profiling show that FDXR potentiates fatty acid oxidation (FAO) through positive regulation of carnitine palmitoyltransferase 1A (CPT1A) expression. Treatment with ER antagonist (tamoxifen) or degrader (fulvestrant) leads to increased expression of FDXR and CPT1A. In line with this finding, we find that FDXR-CPT1A-FAO axis is required for primary and endocrine resistant breast cancer cell growth. Therapeutically,combining endocrine therapy with FAO inhibitor synergistically reduces primary and endocrine resistant breast cancer cell growth, thus providing a potential combinatory treatment for ER+ breast cancer. We used microarrays to be able to elucidate to some extent the gene regulatory mechanisms of FDXR regulating breast cancer metabolism.

2023-05-24 | GSE217902 | GEO

An obesogenic FTO allele causes accelerated development, growth and insulin resistance in human skeletal muscle cells

Project description:Human GWAS have shown that obesogenic FTO polymorphisms correlate with lean mass, but the mechanisms have remained unclear. It is counterintuitive because lean mass is inversely correlated with obesity and metabolic diseases. Here, we use CRISPR to knock-in FTOrs9939609-A into hESC-derived tissue models, to elucidate potentially hidden roles of FTO during development. We find that among human tissues , FTOrs9939609-A most robustly affect human muscle progenitors’ proliferation, differentiation, senescence, thereby accelerating muscle developmental and metabolic aging. An edited FTOrs9939609-A allele over-stimulates insulin/IGF signaling via increased muscle-specific enhancer H3K27ac, FTO expression and m6A demethylation of H19 lncRNA and IGF2 mRNA, with excessive insulin/IGF signaling leading to insulin resistance upon replicative aging or exposure to high fat diet. This FTO-m6A-H19/IGF2 circuit may explain paradoxical GWAS findings linking FTOrs9939609-A to both leanness and obesity. Our results provide a proof-of-principle that CRISPR-hESC-tissue platforms can be harnessed to resolve puzzles in human metabolism.

2024-10-15 | GSE262261 | GEO

Multi-omic analysis identifies metabolic biomarkers for early detection of breast cancer and prediction of therapeutic responses

Project description:Reliable blood-based tests for identifying early-stage breast cancer remain elusive. Employing single-cell transcriptomic sequencing analysis, we illustrate a close correlation between nucleotide metabolism in breast tumor cells and activation of regulatory T cells (Tregs) in the tumor microenvironment, which show distinction in subtypes of triple-negative breast cancer (TNBC) and non-TNBC patients and likely to impact on prognosis of BC through A2AR-Treg pathway. Combining machine learning with absolute quantitative plasma metabolomics, we establish an effective diagnostic model for early-stage breast cancer, utilizing a four-metabolite panel including two nucleoside metabolites, inosine and uridine. This metabolomics study, involving 1111 participants, demonstrates high accuracy across training, test, and independent validation cohorts. Surprisingly, inosine and uridine prove predictive of the response to neoadjuvant chemotherapy (NAC) in TNBC patients. This study deepens the understanding of nucleotide metabolism in development of breast cancer and introduces a promising non-invasive approach with low radiation exposure for early breast cancer detection and predicting NAC response in TNBC patients.

2024-08-03 | GSE268662 | GEO

WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

Project description:Purpose: Metastatic breast cancer remains a major cause of cancer related deaths in women and there are few effective therapies against this advanced disease. Using an in vivo genetic screen, we identified WDR5 as an actionable epigenetic regulator that is required for metastatic progression in models of triple-negative breast cancer. Here we profile the transcriptome of metastatic breast cancer cells following WDR5 knockdown Methods: RNA-Seq analysis of breast cancer cell lines MDA-MB-231 LM2, BoM, BrM3 Results: We identified that WDR5 directly controls the expression of ribosomal genes. Conclusions: We found that WDR5 is a potential target in breast cancer metastasis

2022-08-31 | GSE196666 | GEO

Multi-treatment models for breast cancer

Project description:Multi-treatment models for breast cancer

| PRJNA563821 | ENA

Preclinical model of obesity and ER-positive breast cancer

Project description:Here, we developed a mouse model of diet induced obesity that is graft competent. In this model, we grew an ER-positive breast cancer patient derived tumor. Following ovariectomy and estrogen deprivation therapy, tumors continued to grow in obese but not lean mice. RNAsequencing analysis was performed on tumors from estrogen-supplemented lean mice, and from lean and obese mice after estrogen deprivation. This analysis identified fibroblast growth factor receptor signaling as a potential driver of tumor progression in the context of obesity.

2019-03-01 | GSE110644 | GEO

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