Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oncogenic KRAS induces arginine auxotrophy in non-small cell lung cancer and confers a therapeutic vulnerability to SLC7A1 inhibition

ABSTRACT: Oncogenic KRAS induces arginine auxotrophy in non-small cell lung cancer and confers a therapeutic vulnerability to SLC7A1 inhibition

PROVIDER: PRJNA1066766 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR27646828_1.fastq.gz	Fastqsanger.gz
	SRR27646828_2.fastq.gz	Fastqsanger.gz
	SRR27646829_1.fastq.gz	Fastqsanger.gz
	SRR27646829_2.fastq.gz	Fastqsanger.gz
	SRR27646830_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Oncogenic KRAS induces arginine auxotrophy in non-small cell lung cancer and confers a therapeutic vulnerability to SLC7A1 inhibition

Project description:The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer, yet our understanding about the regulatory mechanisms for this pathway in different types of cancer is very limited. In this study, we discover that oncogenic activation of KRAS in non-small cell lung cancer (NSCLC) silences the expression of arginosuccinate synthase 1 (ASS1), a urea cycle enzyme catalyzing the production of arginine from aspartate and citrulline, and thereby diverts the utilization of aspartate to pyrimidine synthesis to meet the high demand for DNA replication in KRAS-mutant NSCLC. Specifically, KRAS signaling facilitates a hypo-acetylated state in the promoter region of ASS1 gene in a histone deacetylase 3 (HDAC3)-dependent manner, which in turn impedes the recruitment of the transcription factor c-MYC for ASS1 transcription. ASS1 suppression in KRAS-mutant NSCLC cancer cells impairs the biosynthesis of arginine and renders growth dependency on SLC7A1, an arginine transmembrane transport, to import extracellular arginine. Depletion of SLC7A1 in both patient-derived organoid and xenograft models obtains a substantial therapeutic benefit in inhibiting KRAS-driven NSCLC growth. Together, our findings uncover a new role of oncogenic KRAS in rewiring urea cycle metabolism and identify SLC7A1-mediated arginine uptake as a therapeutic vulnerability in treating KRAS-mutant NSCLC.

2024-01-20 | GSE253688 | GEO

ASS1 deficiency defines a therapeutic vulnerability in Philadelphia chromosome-positive acute lymphoblastic leukaemia

Project description:Amino acid deprivation with L-asparaginase is a cornerstone of treatment in acute lymphoblastic leukaemia (ALL), but clinical challenges limit its use in adults. Deficiency in the enzyme argininosuccinate synthase (ASS1-low) confers arginine auxotrophy, defining a dependence on extracellular arginine, and represents an analogue metabolic vulnerability that is targetable through arginine deprivation. We analysed transcriptomic data across >550 adult B-ALL cases to establish clinico-biologic characteristics of low ASS1 expression identifying the Philadelphia chromosome-positive (Ph+) ALL subgroup as a stereotypical arginine auxotroph within molecularly diverse B-ALL. Functionally, arginine deprivation with pegargiminase induced robust apoptosis in both Ph+ ALL cell lines and primary samples in an ASS1 dependant manner and was highly effective as a monotherapy treatment in independent Ph+ ALL patient derived xenografts. Mechanistically, arginine deprivation induces endoplasmic reticulum stress mediated apoptosis which was orthogonal to tyrosine kinase inhibition (TKI) mediated outcomes. Using in vitro and in vivo models of non-genetically mediated TKI-resistance, we demonstrate pegargiminase and TKI combinations robustly eradicates TKI resistant leukaemia. Thus, we establish ASS1 deficiency (ASS1-low) as a therapeutically actionable vulnerability in Ph+ ALL and a strategy to bypass TKI-resistance, supporting clinical evaluation of arginine deprivation as a novel adjunct to chemotherapy-free treatment.

2026-05-25 | GSE330924 | GEO

Activation-induced SLC7A1 expression enhances T cell sensitivity to cGAMP-mediated STING signaling [T_cells_RNA_Seq]

Project description:STING agonists are promising innate immune therapies and can synergize with adaptive immune checkpoint blockade therapies for cancer treatment, but their effectiveness is limited by the toxicity to activated T cells. How STING agonists such as cGAMP and its analogs enter and induce STING activation and toxicity in T cells is unclear despite known transporters for other cell types. Here, we identify the cationic amino acid transporter SLC7A1 as a cGAMP transporter in activated primary mouse and human T cells. T cells upregulate this transporter upon activation to meet their high metabolic demand, but this comes at the cost of enabling increased transport and toxicity of cGAMP. We identified distinct residues in SLC7A1 that mediate cGAMP and arginine activity suggesting that cGAMP transport may be separable from arginine uptake. These findings suggest that modulation of SLC7A1 may influence T cell susceptibility to cGAMP and its analogs.

2026-05-21 | GSE325689 | GEO

Activation-induced SLC7A1 expression enhances T cell sensitivity to cGAMP-mediated STING signaling [U937_DOX_RNA_Seq]

2026-05-21 | GSE325690 | GEO

Identification of SLC7A1 as a potential therapeutic target for high-grade meningioma

Project description:High-grade meningioma remains a therapeutic challenge to medical oncologists. It is urgent to uncover novel molecular targets. Solute carrier family 7 member 1 (SLC7A1) was highly expressed in high-grade meningioma and associated with poor prognosis of patients. SLC7A1 knockdown significantly inhibited the proliferation and invasion of malignant meningioma cells. In addition, the small-molecule drug AZ628 showed an excellent antiproliferative effect on malignant meningioma cells, indicating that it is a potential antitumor drug for high-grade meningioma. Our study revealed the essential roles of SLC7A1 in the malignant progression of meningioma, suggesting SLC7A1 as a potential antitumor target for high-grade meningioma.

2025-09-27 | GSE244554 | GEO

Protein Arginine Methyltransferase 1 is therapeutic vulnerability in Multiple Myeloma

Project description:Protein Arginine Methyltransferase 1 is therapeutic vulnerability in Multiple Myeloma

| PRJNA983271 | ENA

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers

Project description:A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers

| PRJNA487264 | ENA

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [inhibitors]

Project description:A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [inhibitors]

| PRJNA487269 | ENA

A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [HOXC10]

Project description:A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS mutant lung cancers [HOXC10]

| PRJNA487268 | ENA

Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction

Project description:Defective arginine synthesis, due to the silencing of argininosuccinate synthase 1 (ASS1), is a common metabolic vulnerability in cancer, known as arginine auxotrophy. Understanding how arginine depletion kills arginine-auxotrophic cancer cells will facilitate the development of anti-cancer therapeutic strategies. Here we show that depletion of extracellular arginine in arginine-auxotrophic cancer cells causes mitochondrial distress and transcriptional reprogramming. Mechanistically, arginine starvation induces asparagine synthetase (ASNS), depleting these cancer cells of aspartate, and disrupting their malate-aspartate shuttle. Supplementation of aspartate, depletion of mitochondria, and knockdown of ASNS all protect the arginine-starved cells, establishing the causal effects of aspartate depletion and mitochondrial dysfunction on the arginine starvation-induced cell death. Furthermore, dietary arginine restriction reduced tumor growth in a xenograft model of ASS1-deficient breast cancer. Our data challenge the view that ASNS promotes homeostasis, arguing instead that ASNS-induced aspartate depletion promotes cytotoxicity, which can be exploited for anti-cancer therapies.

2019-11-07 | MTBLS745 | MetaboLights

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