Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer [CRISPR Screen]

ABSTRACT: Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer [CRISPR Screen]

PROVIDER: PRJNA666653 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12748038.fastq.gz	Fastqsanger.gz
	SRR12748039.fastq.gz	Fastqsanger.gz
	SRR12748040.fastq.gz	Fastqsanger.gz
	SRR12748041.fastq.gz	Fastqsanger.gz
	SRR12748042.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer [CRISPR Screen]

Project description:Purpose: Modeling microenvironmental influences in cell culture has been challenging, and technical limitations have hampered the comprehensive study of tumor-specific metabolism in vivo. To systematically interrogate metabolic vulnerabilities in PDA, we employed parallel CRISPR-Cas9 genetic screens using both in vivo and in vitro model systems. Methods: A custom library of lentiviral vectors encoding ~18,000 sgRNAs targeting ~3,000 mouse metabolic genes and performed CRISPR-Cas9 screens using a C/57BL6 (B6) mouse pancreatic cancer cell line derived from a KrasG12D-driven autochthonous PDA model. After transduction and selection, parallel screens were performed by in vitro passage or tumor implantation subcutaneously into the flanks of syngeneic hosts. Genomic DNA was then harvaested in vitro after 7 passages (21 days in culture) and in vivo 21 days after implantation. Results: This work revealed striking overlap of in vivo metabolic dependencies with those in vitro, validating that standard 2D culture conditions are a reliable system for studying cancer metabolism. Moreover, we identified that intercellular nutrient sharing can mask cancer dependencies in pooled screening experiments, highlighting an important limitation of this approach to study tumor metabolism Conclusions:Our work demonstrates the power of genetic screening approaches to define the compendium of in vivo metabolic dependencies in PDA and highlights critical metabolic pathways that may have therapeutic utility.

2020-10-01 | GSE158789 | GEO

Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer [RNA-Seq]

Project description:Purpose: Modeling microenvironmental influences in cell culture has been challenging, and technical limitations have hampered the comprehensive study of tumor-specific metabolism in vivo. To systematically interrogate metabolic vulnerabilities in PDA, we employed parallel CRISPR-Cas9 genetic screens using both in vivo and in vitro model systems. Methods: 2D culture collected 3 days after plating grown in DMEM, 10%fbs, 1%p/s. 3D culture collected 3 days after plating grown in DMEM, 10%fbs, 1% p/s, 5% matrigel. Tumors were collected from orthotopic injections collected at endpoint of experiment. Results: This work revealed striking overlap of in vivo metabolic dependencies with those in vitro, validating that standard 2D culture conditions are a reliable system for studying cancer metabolism. Moreover, we identified that intercellular nutrient sharing can mask cancer dependencies in pooled screening experiments, highlighting an important limitation of this approach to study tumor metabolism Conclusions: Our work demonstrates the power of genetic screening approaches to define the compendium of in vivo metabolic dependencies in PDA and highlights critical metabolic pathways that may have therapeutic utility.

2020-10-01 | GSE158657 | GEO

Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer.

Project description:Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer characterized by complex metabolic adaptations that promote survival in a severely hypoxic and nutrient-limited tumor microenvironment (TME). Modeling microenvironmental influences in cell culture has been challenging, and technical limitations have hampered the comprehensive study of tumor-specific metabolism in vivo. To systematically interrogate metabolic vulnerabilities in PDA, we employed parallel CRISPR-Cas9 screens using in vivo and in vitro systems. This work revealed striking overlap of in vivo metabolic dependencies with those in vitro. Moreover, we identified that intercellular nutrient sharing can mask dependencies in pooled screens, highlighting a limitation of this approach to study tumor metabolism. Furthermore, metabolic dependencies were similar between 2D and 3D culture, although 3D culture may better model vulnerabilities that influence certain oncogenic signaling pathways. Lastly, our work demonstrates the power of genetic screening approaches to define in vivo metabolic dependencies and pathways that may have therapeutic utility.

| S-EPMC7790858 | biostudies-literature

Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer

Project description:Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer

| PRJNA666645 | ENA

An in vivo CRISPR screen identifies stepwise genetic dependencies of metastatic progression

Project description:In vivo genome-wide loss-of-function CRISPR screen identifies critical genes required for individual steps of the metastatic cascade in human CTC-derived xenografts, suggesting novel drivers and vulnerabilities of breast cancer metastasis.

2022-01-27 | GSE138813 | GEO

CRISPR screen

Project description:CRISPR screen

2023-04-25 | OEX00023089 | NODE

CRISPR-screen

Project description:CRISPR screen

2025-03-27 | OEX00031362 | NODE

CRISPR-screen

Project description:CRISPR screen

2025-05-29 | OEX00031508 | NODE

Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer [RNA-Seq]

Project description:Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer [RNA-Seq]

| PRJNA666652 | ENA

CRISPR metabolic screen identifies ATM and KEAP1 as targetable genetic vulnerabilities in solid tumors.

Project description:Cancer treatments targeting DNA repair deficiencies often encounter drug resistance, possibly due to alternative metabolic pathways that counteract the most damaging effects. To identify such alternative pathways, we screened for metabolic pathways exhibiting synthetic lethality with inhibition of the DNA damage response kinase Ataxia-telangiectasia-mutated (ATM) using a metabolism-centered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 library. Our data revealed Kelch-like ECH-associated protein 1 (KEAP1) as a key factor involved in desensitizing cancer cells to ATM inhibition both in vitro and in vivo. Cells depleted of KEAP1 exhibited an aberrant overexpression of the cystine transporter SLC7A11, robustly accumulated cystine inducing disulfide stress, and became hypersensitive to ATM inhibition. These hallmarks were reversed in a reducing cellular environment indicating that disulfide stress was a crucial factor. In The Cancer Genome Atlas (TCGA) pan-cancer datasets, we found that ATM levels negatively correlated with KEAP1 levels across multiple solid malignancies. Together, our results unveil ATM and KEAP1 as new targetable vulnerabilities in solid tumors.

| S-EPMC9963842 | biostudies-literature

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