Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Frequent 4EBP1 amplification induces synthetic dependence on FGFR signaling in cancer

ABSTRACT: Frequent 4EBP1 amplification induces synthetic dependence on FGFR signaling in cancer

PROVIDER: PRJNA811788 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR18189900_1.fastq.gz	Fastqsanger.gz
	SRR18189900_2.fastq.gz	Fastqsanger.gz
	SRR18190000_1.fastq.gz	Fastqsanger.gz
	SRR18190000_2.fastq.gz	Fastqsanger.gz
	SRR18189901_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 429

Similar Datasets

Frequent 4EBP1 amplification induces synthetic dependence on FGFR signaling in cancer

Project description:The eIF4E translation initiation factor has oncogenic properties and concordantly, the inhibitory eIF4E-binding protein (4EBP1) is considered a tumor suppressor. The exact molecular effects of 4EBP1 activation in cancer are still unknown. Surprisingly, 4EBP1 is a target of genomic copy number gains (Chr. 8p11) in breast and lung cancer. We notice that 4EBP1 gains are genetically linked to gains in neighboring genes including WHSC1L1 and FGFR1. Our results show that FGFR1 gains act to attenuate the function of 4EBP1 via PI3K mediated phosphorylation at Thr37/46, Ser65, and Thr70 sites. This implies that not 4EBP1 but instead FGFR1 is the genetic target of Chr. 8p11 gains in breast and lung cancer. Accordingly, these tumors show increased sensitivity to FGFR1 and PI3K inhibition and this is a therapeutic vulnerability through restoring the tumor-suppressive function of 4EBP1. Ribosome profiling reveals genes involved in insulin signaling, glucose metabolism, and inositol pathway to be the relevant translational targets of 4EBP1. These mRNAs are among the top 200 translation targets and are highly enriched for structure and sequence motifs in their 5’UTR that depends on the 4EBP1-EIF4E activity. In summary, we identify the translational targets of 4EBP1-EIF4E that facilitate the tumor suppressor function of 4EBP1 in cancer.

2022-03-05 | GSE197735 | GEO

Frequent 4EBP1 Amplification Induces Synthetic Dependence on FGFR Signaling in Cancer.

Project description:The eIF4E translation initiation factor has oncogenic properties and concordantly, the inhibitory eIF4E-binding protein (4EBP1) is considered a tumor suppressor. The exact molecular effects of 4EBP1 activation in cancer are still unknown. Surprisingly, 4EBP1 is a target of genomic copy number gains (Chr. 8p11) in breast and lung cancer. We noticed that 4EBP1 gains are genetically linked to gains in neighboring genes, including WHSC1L1 and FGFR1. Our results show that FGFR1 gains act to attenuate the function of 4EBP1 via PI3K-mediated phosphorylation at Thr37/46, Ser65, and Thr70 sites. This implies that not 4EBP1 but instead FGFR1 is the genetic target of Chr. 8p11 gains in breast and lung cancer. Accordingly, these tumors show increased sensitivity to FGFR1 and PI3K inhibition, and this is a therapeutic vulnerability through restoring the tumor-suppressive function of 4EBP1. Ribosome profiling reveals genes involved in insulin signaling, glucose metabolism, and the inositol pathway to be the relevant translational targets of 4EBP1. These mRNAs are among the top 200 translation targets and are highly enriched for structure and sequence motifs in their 5'UTR, which depends on the 4EBP1-EIF4E activity. In summary, we identified the translational targets of 4EBP1-EIF4E that facilitate the tumor suppressor function of 4EBP1 in cancer.

| S-EPMC9139685 | biostudies-literature

Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [scRNA-seq]

Project description:Alterations in Fibroblast growth factor receptor proteins frequently occur as oncogenes in many cancers. FGFR alterations have been reported in a subset of pediatric gliomas, representing a therapeutic target for precision medicine approaches. We performed a genomic analysis of 13,659 gliomas and found that 4.5% harbor FGFR alterations including structural variants and single nucleotide variants. FGFR family members are differentially enriched by age, tumor grade, and histological subtype. FGFR1 alterations are most frequent in pediatric gliomas, particularly pediatric low-grade gliomas, while FGFR3 drivers were associated with adult gliomas. In vitro and in vivo functional studies confirm FGFR1 alterations to be sufficient to activate MAPK and mTOR signaling, drive gliomagenesis and activate neuronal transcriptional programs. FGFR1-driven models showed sensitivity to MAPK pathway inhibitors, including panFGFR inhibitors that are FDA approved for use in other cancers. While early FGFR inhibition was sufficient to prolong survival of mice bearing FGFR-driven xenografts, this was insufficient to induce cures. Similarly, review of patients treated with currently available MAPK pathway or FGFR inhibitors revealed modest responses. This study provides key insights into the biology of FGFR1-altered gliomas and potential strategies to therapeutically target them.

2025-05-16 | GSE273990 | GEO

Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [RNA-seq]

2025-05-16 | GSE273989 | GEO

Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [RNA-Seq 2]

2025-05-16 | GSE286565 | GEO

Role of 4EBP1/2 in the response to glucose deprivation

Project description:We investigated the function of the mTORC1 substrates and mRNA translation regulators 4EBP1/2 in the response to glucose deprivation. We uncovered that targeting 4EBP1/2 expression had a direct impact on the survival rates of cells challenged with glucose deprivation. To further define the mechanisms underlying 4EBP1/2 function under glucose deprivation, we conducted a proteomics analysis of HEK293 shRNA control and HEK293 shRNA 4EBP1/2 grown in basal media or under glucose deprivation (1 mM glucose containing media) for 30 hours.

2024-03-28 | PXD040931 | Pride

Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas

Project description:Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas

| PRJNA1144947 | ENA

Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5′TOP mRNAs [4EBP1/2]

Project description:To investigate the changes in gene expression upon loss of 4EBP1/2, we performed RNA-seq and differential gene expression analysis on WT and derived 4EBP1/2 KD cell lines. The canonical and 5′TOP mRNA cell lines used for single-molecule imaging were treated as biological replicates for the differential gene expression analysis.

2024-01-15 | GSE233182 | GEO

Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [scRNA-seq]

Project description:Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [scRNA-seq]

| PRJNA1144422 | ENA

Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [RNA-seq]

Project description:Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas [RNA-seq]

| PRJNA1144419 | ENA