Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis

ABSTRACT: Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis

PROVIDER: PRJNA1258287 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR33415404.fastq.gz	Fastqsanger.gz
	SRR33415405.fastq.gz	Fastqsanger.gz
	SRR33415406.fastq.gz	Fastqsanger.gz
	SRR33415407.fastq.gz	Fastqsanger.gz
	SRR33415408.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis

Project description:Lipids are essential components of cancer cells due to their structural and signaling roles. To meet metabolic demands, many cancers take up extracellular lipids; however, how these lipids contribute to cancer growth and progression remains poorly understood. Here, using functional genetic screens, we identify lipoprotein uptake—the primary mechanism for lipid transport in circulation—as a key determinant of ferroptosis sensitivity in cancer. Lipoprotein supplementation robustly inhibits ferroptosis across diverse cancer types, primarily through the delivery of α-tocopherol (α-toc), the most abundant form of vitamin E in human lipoproteins. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) linked to cell-surface proteoglycans. Disrupting GAG biosynthesis or acutely degrading surface GAGs reduces lipoprotein uptake, sensitizes cancer cells to ferroptosis, and impairs tumour growth in mice. Notably, human clear cell renal cell carcinomas, a lipid-rich malignancy, exhibit elevated levels of chondroitin sulfate and increased lipoprotein-derived α-toc compared to normal kidney tissue. Altogether, our work establishes lipoprotein uptake as a critical anti-ferroptotic mechanism in cancer and implicates GAG biosynthesis as a therapeutic target.

2025-05-06 | GSE296260 | GEO

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis

Project description:Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains unknown. Here, we report that major facilitator superfamily domain containing 7C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency leads to mitochondrial dysfunction and lipid remodeling caused by increased fatty acid uptake and decreased consumption, the excess accumulation of lipids sensitizes cells to peroxidation and ferroptosis. Moreover, systematic delivery of MFSD7C mRNA-loaded nanoparticles to the lungs effectively prevented lung injury in mice with hemolysis. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

2024-02-08 | GSE252686 | GEO

A sexually dimorphic hepatic cycle of very low density lipoprotein uptake and assembly

Project description:A sexually dimorphic hepatic cycle of very low density lipoprotein uptake and assembly

| PRJNA1022779 | ENA

Darapladib, an inhibitor of Lp-PLA2, sensitises cancer cells to ferroptosis by remodelling lipid metabolism

Project description:Arachidonic and adrenic acids in the membrane play key roles in ferroptosis, but how these fatty acids are manipulated in cells is largely unknown. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen revealed that darapladib, an inhibitor of Lp-PLA2, synergistically induced ferroptosis in the presence of GPX4 inhibitors. Notably, darapladib was able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, Lp-PLA2 was located in the membrane and cytoplasm and suppressed ferroptosis, suggesting the critical role of intracellular Lp-PLA2. Lipidomic analysis showed that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriched phosphatidylethanolamine (PE) species and reduced lysophosphatidylethanolamine (lysoPE) species. Moreover, combination treatment with darapladib and PACMA31, a GPX4 inhibitor, efficiently inhibited tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.

2023-10-24 | PXD044002 | Pride

MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Project description:Analysis of ferroptosis markers from cells isolated from neuroblastoma orthotopic xenograft mouse model. We combine simultaneous inhibition of cysteine uptake and transsulfuration in xenograft model using SK-N-DZ cell line. We treated the mice with IKE and PPG together with genetic targeting of GPX4 activity. At the end of the treatment, transcriptional profiling of residual small tumors revealed induction of ferroptosis markers after combined inhibition of cystine uptake/cysteine synthesis and GPX4 as compared to tumors treated with vehicle control.

2022-01-05 | GSE192976 | GEO

VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis

Project description:Mitochondria play a critical role in initiating and amplifying ferroptosis. VDAC1 embedded in the mitochondrial outer membrane, exerts a crucial role in regulation of ferroptosis. However, the mechanisms of VDAC1 oligomerization in regulating ferroptosis are not well elucidated. Here, we identified that VSTM2L, a novel VDAC1 binding protein, is positively associated with prostate cancer (PCa) progression, and a key regulator of ferroptosis. Moreover, VSTM2L knockdown in PCa cells enhanced the sensibility of RSL3-induced ferroptosis. Mechanistically, VSTM2L forms complex with VDAC1 and HK2, enhancing their binding affinity and preventing VDAC1 oligomerization, thereby inhibiting ferroptosis and maintaining mitochondria homeostasis in vitro and in vivo. Collectively, our findings reveal a pivotal role for VSTM2L in driving ferroptosis resistance and highlight its potential as a ferroptosis-inducing therapeutic target for the treatment of PCa.

2025-05-07 | PXD052173 | Pride

SLC6A8-mediated creatine uptake suppresses ERK2-FSP1 signaling and induces ferroptosis in colorectal cancer

Project description:We discovered, through untargeted metabolomics, that creatine promotes ferroptosis in colorectal cancer. Our study identifies ERK2 as a creatine sensor that mediates active FSP1 and ferroptosis resistance, and highlights the potential of targeting tumor SLC6A8 for cancer treatment.

2025-09-05 | GSE285466 | GEO

SLC6A8-mediated creatine uptake suppresses ERK2-FSP1 signaling and induces ferroptosis in colorectal cancer

Project description:SLC6A8-mediated creatine uptake suppresses ERK2-FSP1 signaling and induces ferroptosis in colorectal cancer

| PRJNA1203678 | ENA

FXR protects cisplatin-induced AKI via transcriptional regulation of ferroptosis.

Project description:Farnesoid X receptor (FXR, also known as NR1H4) is crucial to nephroprotective in several kinds of kidney diseases, including obesity, diabetes, aging, acute kidney injury and chronic kidney disease. FXR plays a key role in maintaining cholesterol and bile acid levels and is highly expressed in the liver, intestine and kidneys. In kidney diseases, it is reported that FXR has anti-lipogenic, anti‐inflammatory, antifibrotic, and antioxidant functions. Here, using genomics analysis, we investigated whether FXR attenuates cisplatin-induced AKI through the regulation of ferroptosis. The increased blood urea nitrogen, serum creatinine and ferroptotic responses in cisplatin-induced AKI mice were attenuated by treatment with FXR agonist, GW4064, while those were exacerbated in FXR knockout mice. Using RNA-sequencing analysis, we found novel target genes for FXR associated with ferroptosis. FXR agonist treatment increases lipid and glutathione metabolic gene expression and decreases cell death genes expression. This study identifies transcriptional regulation of ferroptosis by FXR as a potential therapeutic target for cisplatin-induced AKI.

2022-07-06 | GSE193860 | GEO

Sex differences in the expression and function of hepatic very low-density lipoprotein receptor during protein deficiency in mice

Project description:Very low-density lipoprotein (VLDL) receptor (VLDLR), a member of the low-density lipoprotein receptor family, is responsible for VLDL uptake in peripheral tissues. We reported that significant increase in hepatic VLDLR levels following protein restriction in male mice does not contribute to hepatic fat accumulation, indicating that VLDLR may have hitherto unknown functions. Here, we used RNA-sequencing analysis of liver samples to analysis the effects of protein restriction on hepatic VLDLR in male and female mice.

2024-02-27 | GSE259313 | 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