Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selective abrogation of S6K2 maps lipid homeostasis as a survival vulnerability in MAPKi-resistant NRAS-mut melanoma

ABSTRACT: These data support our manuscript "Selective abrogation of S6K2 maps lipid homeostasis as a survival vulnerability in MAPKi-resistant NRAS-mut melanoma". Proteomics was performed for M93-047 melanoma cells expressing vector control, S6K1 shRNA knockdown or S6K2 shRNA knockdown.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jessie Villanueva

PROVIDER: MSV000083480 | MassIVE | Mon Feb 25 08:57:00 GMT 2019

SECONDARY ACCESSION(S): PXD012875

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

An acquired vulnerability of drug resistant melanoma with therapeutic potential

Project description:An acquired vulnerability of drug resistant melanoma with therapeutic potential

| PRJNA436000 | ENA

Persister state-directed transitioning and vulnerability in melanoma

Project description:Persister state-directed transitioning and vulnerability in melanoma

| PRJNA485951 | ENA

Persister state-directed transitioning and vulnerability in melanoma

Project description:Persister state-directed transitioning and vulnerability in melanoma

| PRJNA574414 | ENA

Lipid droplets are a metabolic vulnerability in melanoma

Project description:Lipid droplets are a metabolic vulnerability in melanoma

| PRJNA831276 | ENA

Persister state-directed transitioning and vulnerability in melanoma

Project description:Persister state-directed transitioning and vulnerability in melanoma

| PRJNA706426 | ENA

Lipid droplets are a metabolic vulnerability in melanoma

Project description:Melanoma exhibits numerous transcriptional cell states including neural crest-like cells as well as pigmented melanocytic cells. How these different cell states relate to distinct tumorigenic phenotypes remains unclear. Here, we use a zebrafish melanoma model to identify a transcriptional program linking the melanocytic cell state to a dependence on lipid droplets, the specialized organelle responsible for lipid storage. Single-cell RNA-sequencing of these tumors show a concordance between genes regulating pigmentation and those involved in lipid and oxidative metabolism. This state is conserved across human melanoma cell lines and patient tumors. This melanocytic state demonstrates increased fatty acid uptake, an increased number of lipid droplets, and dependence upon fatty acid oxidative metabolism. Genetic and pharmacologic suppression of lipid droplet production is sufficient to disrupt cell cycle progression and slow melanoma growth in vivo. Because the melanocytic cell state is linked to poor outcomes in patients, these data indicate a metabolic vulnerability in melanoma that depends on the lipid droplet organelle.

2023-03-26 | GSE201378 | GEO

Proteomics of murine melanoma tumor cells upon sphingosine kinase-1 inhibition

Project description:In order to assess the impact of sphingosine kinase-1 (SK1) expression on melanoma growth, stable SK1 knockdown cells were generated by shRNA, using Yumm 1.7 cells derived from spontaneous murine melanoma driven by Braf activation as well as Pten and Cdkn2a inactivation. Two cell lines silenced for SK1 (shSK1(1) and shSK1(2)) were obtained.

2019-12-17 | PXD016535 | Pride

The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma

Project description:The AhR-SRC axis as a therapeutic vulnerability in BRAFi-resistant melanoma

| PRJNA701428 | ENA

Genome-wide maps of chromatin state in KMT2D Knockout and KMT2D WT melanoma in mice

Project description:Somatic mutations in various epigenetic regulators, including histone methyltransferases KMT2C and KMT2D, have emerged as important cancer-driving events. However, the mechanism of action and therapeutic vulnerability imparted by these mutations remain poorly understood. We identified KMT2D and 8 other epigenetic regulators as potential suppressors to melanoma initiation through an in vivo pooled epigenome-focused RNAi screen. Loss of KMT2D, which exhibits somatic mutations in human melanoma and other cancers, drastically enhanced melanoma progression in xenograft models and a BRAFV600E-driven genetically engineered mouse model of melanoma. Epigenome profiling of 6 histone marks and chromatin state alterations showed substantial reprogramming of H3K4me1- and H3K27ac-marked active enhancer states in KMT2D mutant tumors. Energy metabolic pathways such as glycolysis, OxPhos and TCA/electron transport showed high degree of deregulation which was confirmed with metabolic profiling. Pharmacological abrogation of glycolysis led to reduced proliferation and tumorigenesis preferentially in KMT2D mutant cells. Mechanistically, we find that enhancer loss at IGFBPs increases IGF signaling and downstream AKT phosphorylation that leads to upregulation of metabolic pathways rendering KMT2D mutant cells dependent on these energy metabolism pathways for their higher growth potential. Overall, we present evidence that KMT2D mutations promote tumorigenesis by reprogramming energy metabolism pathways through enhancer reprogramming.

2020-11-16 | GSE116851 | GEO

Combined inhibition of MNK signaling and BET proteins reveals TGM2 as a novel vulnerability in melanoma

Project description:Melanoma is the deadliest form of skin cancer. MAPK-targeted therapies (MAPKi) and immune checkpoint inhibitors (ICI) have shown clinical benefit but are limited by resistance mechanisms that remain poorly defined. MNK1/2 inhibitors (MNKi) have shown promising effects in pre-clinical tumor models, particularly in melanoma. Herein, we find that bromodomain and extra-terminal domain protein inhibitors (BETi) in combination with MNKi reduce the proliferation of melanoma cells, including cells with acquired MAPKi resistance. Transcriptomic and proteomic analyses reveal that tissue transglutaminase TGM2 and inhibition of FAK activation are downstream effectors of this combination. We further demonstrate that TGM2 is overexpressed in MAPKi-resistant melanoma cells and that silencing TGM2 inhibits the proliferation of therapy-resistant melanoma cells. Our results introduce TGM2 as a new vulnerability in therapy-resistant melanoma development and suggest that a combination of MNKi and BETi may address the clinical need for novel therapies targeting unresponsive and drug-resistant melanoma.

2024-10-01 | PXD044698 | Pride

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