Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157745 | GEO | 2020/11/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [ChIP-Seq]

Project description:Circulating tumor cells (CTCs) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastatic outgrowth. Here we show that CTCs from patients with BRAF-mutant melanoma coordinately upregulate both lipogenesis and iron homeostasis pathways. In clonally-derived cultures of melanoma CTCs these pathways are correlated with both intrinsic and acquired resistance to BRAF inhibitors. The lipogenesis regulator SREBF2 directly induces transcription of the iron carrier Transferrin (TF), reducing intracellular iron pools, reactive oxygen species (ROS) and lipid peroxidation, and conferring resistance to both BRAF inhibitors and inducers of ferroptosis. Knockdown of endogenous TF impairs tumor formation by melanoma CTCs, and their tumorigenic defects are partially rescued by the lipophilic anti-oxidants Ferrostatin-1 and Vitamin E. In a cohort of patient-derived melanoma CTCs, single cell RNA-seq identifies a subset with high lipogenic, iron metabolic and proliferative signatures, which are correlated with adverse clinical outcome, irrespective of treatment regimen. Thus, SREBF2-driven iron homeostatic pathways contribute to cancer progression, drug resistance and metastasis.

2020-11-13 | GSE157741 | GEO

The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis.

Project description:Circulating tumor cells (CTC) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from patients with melanoma coordinately upregulate lipogenesis and iron homeostasis pathways. These are correlated with both intrinsic and acquired resistance to BRAF inhibitors across clonal cultures of BRAF-mutant CTCs. The lipogenesis regulator SREBP2 directly induces transcription of the iron carrier Transferrin (TF), reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, thereby conferring resistance to inducers of ferroptosis. Knockdown of endogenous TF impairs tumor formation by melanoma CTCs, and their tumorigenic defects are partially rescued by the lipophilic antioxidants ferrostatin-1 and vitamin E. In a prospective melanoma cohort, presence of CTCs with high lipogenic and iron metabolic RNA signatures is correlated with adverse clinical outcome, irrespective of treatment regimen. Thus, SREBP2-driven iron homeostatic pathways contribute to cancer progression, drug resistance, and metastasis. SIGNIFICANCE: Through single-cell analysis of primary and cultured melanoma CTCs, we have uncovered intrinsic cancer cell heterogeneity within lipogenic and iron homeostatic pathways that modulates resistance to BRAF inhibitors and to ferroptosis inducers. Activation of these pathways within CTCs is correlated with adverse clinical outcome, pointing to therapeutic opportunities.This article is highlighted in the In This Issue feature, p. 521.

| S-EPMC7933049 | biostudies-literature

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [TF KD RNA-Seq]

2020-11-13 | GSE157744 | GEO

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [single cell RNA-Seq]

2020-11-13 | GSE157743 | GEO

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [isogenic CTC lines RNA-Seq]

2020-11-13 | GSE157742 | GEO

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis

Project description:The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis

| PRJNA662599 | ENA

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [CTC lines vs tumors and CCLE lines RNA-Seq]

2020-11-13 | GSE157740 | GEO

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [ChIP-Seq]

Project description:The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [ChIP-Seq]

| PRJNA662602 | ENA

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [TF KD RNA-Seq]

Project description:The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [TF KD RNA-Seq]

| PRJNA662605 | ENA

The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [single cell RNA-Seq]

Project description:The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis [single cell RNA-Seq]

| PRJNA662604 | ENA

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