Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [MSK-LX227C]

ABSTRACT: Gene expression in human small cell carinoma PDX models treated with MLN4924

ORGANISM(S): Homo sapiens

PROVIDER: GSE171255 | GEO | 2021/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [FHSC39]

Project description:Gene expression in human small cell carinoma PDX models treated with MLN4924

2021-04-01 | GSE171260 | GEO

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [JHU-LX108]

Project description:Gene expression in human small cell carinoma PDX models treated with MLN4924

2021-04-01 | GSE171250 | GEO

Organoid-based drug screening reveals neddylation as therapeutic target for malignant rhabdoid tumors

Project description:Malignant rhabdoid tumors (MRT) represent one of the most aggressive childhood malignancies. No effective treatment options are available, and prognosis is therefore dismal. Previous studies have demonstrated that tumor organoids capture the heterogeneity of patient tumors and can be used to predict patient therapy response. Here, we perform drug screening on patient-derived normal and tumor organoids to identify MRT-specific therapeutic vulnerabilities. We identify neddylation inhibitor MLN4924 as a potential therapeutic agent. Mechanistically, we find increased neddylation in MRT organoids and tissues and show that MLN4924 induces a cytotoxic response via upregulation of the unfolded protein response. Lastly, we demonstrate in vivo efficacy in an MRT PDX mouse model, in which single agent MLN4924 treatment significantly extends survival. Our study demonstrates that organoids can be used to find drugs selectively targeting tumor cells while leaving healthy cells unharmed and proposes neddylation inhibition as therapeutic strategy in MRT.

2021-06-24 | GSE178737 | GEO

Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas.

Project description:Small cell lung carcinoma (SCLC) is among the most lethal of all solid tumor malignancies. In an effort to identify novel therapeutic approaches for this recalcitrant cancer type, we applied genome-scale CRISPR/Cas9 inactivation screens to cell lines that we derived from a murine model of SCLC. SCLC cells were particularly sensitive to the deletion of NEDD8 and other neddylation pathway genes. Genetic suppression or pharmacological inhibition of this pathway using MLN4924 caused cell death not only in mouse SCLC cell lines but also in patient-derived xenograft (PDX) models of pulmonary and extrapulmonary small cell carcinoma treated ex vivo or in vivo. A subset of PDX models were exceptionally sensitive to neddylation inhibition. Neddylation inhibition suppressed expression of major regulators of neuroendocrine cell state such as INSM1 and ASCL1, which a subset of SCLC rely upon for cell proliferation and survival. To identify potential mechanisms of resistance to neddylation inhibition, we performed a genome-scale CRISPR/Cas9 suppressor screen. Deletion of components of the COP9 signalosome strongly mitigated the effects of neddylation inhibition in small cell carcinoma, including the ability of MLN4924 to suppress neuroendocrine transcriptional program expression. This work identifies neddylation as a regulator of neuroendocrine cell state and potential therapeutic target for small cell carcinomas.

| S-EPMC8168556 | biostudies-literature

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-04-01 | GSE171262 | GEO

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [MSK-LX227C]

Project description:Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [MSK-LX227C]

| PRJNA718861 | ENA

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas

Project description:Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas

| PRJNA718864 | ENA

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [FHSC39]

Project description:Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [FHSC39]

| PRJNA718867 | ENA

Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [JHU-LX108]

Project description:Protein neddylation as a therapeutic target in pulomonary and extrapulonary small cell carcinomas [JHU-LX108]

| PRJNA718858 | ENA

Regulation of stem cell property and drug resistance of cancer cells by targeting transcriptional machinery via inhibition of neddylation

Project description:MLN4924, also known as pevonedistat, is a small molecule inhibitor of NEDD8 activating enzyme (NAE), that inhibits the entire neddylation pathway. As the first-in-class neddylation inhibitor, MLN4924 is currently in Phase I/II clinical trials for anticancer application as a single agent or in combination with chemotherapeutic drugs. MLN4924 has shown impressive anticancer activity by inactivating Cullin-RING ligases (CRLs) to cause accumulation of tumor suppressor substrates. Whether MLN4924 regulates the RNA expression by modulating the levels of transcription factor/repressor remain elusive. In this study, we treated A549 lung cancer cells with MLN4924 at 0.25 or 0.5 µM for 8 or 24 hrs, respectively, followed by RNAseq analysis. Here we found that MLN4924 significantly decreases the SOX2 mRNA level. The mechanistic study revealed that MLN4924 inhibits FBXW2 E3 to cause MSX2 accumulation, which in turn transcriptionally represses SOX2, leading to suppression of stem cell property and sensitization of cancer cells to tamoxifen.

2019-09-14 | GSE134190 | 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