Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting SCD triggers lipotoxicity of cancer cells and enhances anti-tumor immunity in breast cancer brain metastasis mouse models

ABSTRACT: Targeting SCD triggers lipotoxicity of cancer cells and enhances anti-tumor immunity in breast cancer brain metastasis mouse models

PROVIDER: PRJNA1236318 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR32726505.fastq.gz	Fastqsanger.gz
	SRR32726506.fastq.gz	Fastqsanger.gz
	SRR32726507.fastq.gz	Fastqsanger.gz
	SRR32726508.fastq.gz	Fastqsanger.gz

Items per page:

1 - 4 of 4

Similar Datasets

Targeting SCD triggers lipotoxicity of cancer cells and enhances anti-tumor immunity in breast cancer brain metastasis mouse models

Project description:Breast cancer brain metastases (BCBM) are incurable, and new therapies are urgently needed. BCBM upregulate Stearoyl-CoA Desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, suggesting a potential metabolic vulnerability. Here, we test the effect of a brain-penetrant, clinical-stage SCD inhibitor (SCDi) on breast cancer cells and mouse models of BCBM. We show that SCDi markedly reshapes the lipidome of breast cancer cells, resulting in endoplasmic reticulum stress, DNA damage, impaired DNA damage repair, and cytotoxicity. Importantly, SCDi alone or combined with a PARP inhibitor prolongs the survival of BCBM-bearing mice. Furthermore, pharmacological inhibition of SCD enhances antigen presentation by dendritic cells, increases interferon signaling, promotes the infiltration of cytotoxic T cells, and decreases the proportion of exhausted T cells and regulatory T cells in the tumor microenvironment (TME) in a syngeneic mouse model of BCBM. Additionally, SCDi reduces the engagement of immunosuppressive pathways, including the PD-1:PD-L1/PD-L2 and PVR/TIGIT axes in the TME. These findings suggest that SCD inhibition could be an effective strategy to both intrinsically reduce tumor growth and reprogram anti-tumor immunity in the brain microenvironment to treat BCBM.

2025-04-02 | GSE292006 | GEO

Scd-1 deficiency promotes the differentiation of CD8+ T effector

Project description:The impact of various fatty acid types on adaptive immunity remains uncertain, and their roles remain unelucidated. In this study, we showed that the enzyme stearoyl-CoA desaturase-1 (Scd-1) and its resulting compound, oleic acid (OA), have a substantial impact on the transformation of CD8+ naïve T cells into effector T cells. Inactivation of Scd-1 triggers the specialization of CD8+ T cells into the Teff subset, enhancing the effector function and mitochondrial metabolism of Teff cells, and OA can partially counteract this.

2024-01-25 | GSE253770 | GEO

Regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity

Project description:The ability of cancer cells to switch phenotype in response to a dynamic intra-tumor microenvironment is a major barrier to effective therapy. In melanoma, down-regulation of the lineage addiction oncogene MITF (Microphthalmia-associated transcription factor) is a hallmark of the proliferative-to-invasive phenotype switch. Yet how MITF promotes proliferation and suppresses invasion is poorly understood. Here we show that expression of the key lipogenic enzyme stearoyl-CoA desaturase (SCD) is activated by MITF, but suppressed by the stress-responsive transcription factor ATF4. SCD expression is required for MITF-positive melanoma cell proliferation,. By contrast, MITF-low cells express reduced levels of SCD and are insensitive to its inhibition, indicating that cell phenotype dictates response to drugs targeting lipid metabolism. Since SCD suppresses inflammatory signalling and ATF4 expression, the results identify a positive feedback-loop that can maintain an invasive phenotype, uncover a key role for MITF and ATF4 in metabolic reprograming, and reveal fatty acid composition as a driver of melanoma phenotype-switching.

2019-11-19 | PXD010254 | Pride

Activation of SREBP in Alveolar Type II Cells Enhances Lipogenesis Causing Pulmonary Lipotoxicity

Project description:Background: Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids. Results: Activation of SREBP (Sterol Response Element Binding Protein) induced lipogenesis in alveolar epithelial cells, causing neutral lipid accumulation, lung inflammation, and tissue remodeling. Conclusions: The accumulation of neutral lipids in type II epithelial cells and alveolar macrophages caused lung inflammation, consistent with findings in lipid storage disorders. Significance: Pulmonary lipotoxicity may contribute to the pathogenesis of lung dysfunction associated with diabetes, obesity, and other metabolic disorders. Genome-wide transcription profiling comparison between doxycycline-exposed SFTPC-rtTAWT/Tg/(tetO)7CMV-CreWT/Tg/Insig1flox/flox/Insig2-/- mice (i.e., Insig1/2∆/∆ ) and Insig1flox/flox/Insig2-/- . Three independent pooled RNA from isolated lung type 2 cells of each genotype were used.

2012-03-01 | E-GEOD-31797 | biostudies-arrayexpress

NHLBI TOPMed: Outcome Modifying Gene in SCD (OMG-SCD)

Project description:NHLBI TOPMed: Outcome Modifying Gene in SCD (OMG-SCD)

| PRJNA472122 | ENA

NHLBI TOPMed: Outcome Modifying Gene in SCD (OMG-SCD)

Project description:NHLBI TOPMed: Outcome Modifying Gene in SCD (OMG-SCD)

| PRJNA472123 | ENA

Transcriptional regulation of liver lipotoxicity in non-alcoholic steatohepatitis [RNA-seq]

Project description:Non-alcoholic fatty liver disease is continuum of disorders among which non-alcoholic steatohepatitis (NASH) is particularly associated with a negative prognosis. Hepatocyte lipotoxicity is one of the main pathogenic factors of liver fibrosis and NASH. However, the molecular mechanisms regulating this process are poorly understood. Here, we integrated transcriptomic and chromatin accessibility analyses from human liver and mouse hepatocytes to identify lipotoxicity-sensitive transcription factors. We found that several transcription factors that were activated in liver from NASH patients and by mouse hepatocyte lipotoxicity. Notably, the gene expression linked to lipotoxicity closely correlated with transcriptional patters in fibrosis progression in NASH patients. Collectively, our findings uncovered novel molecular insights into lipotoxicity-induced NASH.

2022-07-13 | GSE173735 | GEO

Transcriptional regulation of liver lipotoxicity in non-alcoholic steatohepatitis [ATAC-seq]

2022-07-13 | GSE173734 | GEO

Activation of SREBP in Alveolar Type II Cells Enhances Lipogenesis Causing Pulmonary Lipotoxicity

2012-03-01 | GSE31797 | GEO

Opaque filamentation in Low Phosphate (LP) and Sorbitol (SOR) compared to in SCD

Project description:Act1-Wor1 strain (the opaque strain CAY2903 with constitute WOR1 expression), wildtype white (a/a RBY717); Opaque hyphal formation in liquid LP and SOR compared to SCD; white cells in the same conditions as control. 6 condition experiment: opaque and white cells in LP, SOR and SCD. Used the pool of all conditions as reference.

2013-04-01 | E-GEOD-42963 | 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