PXD016276

PXD016276 is an original dataset announced via ProteomeXchange.

Title	Cell density-dependent ferroptosis in breast cancer is induced by accumulation of polyunsaturated fatty acid-enriched triacylglycerides
Description	Ferroptosis is a regulated form of necrotic cell death caused by iron-dependent phospholipid peroxidation. It can be induced by inhibiting glutathione peroxidase 4 (GPX4), the key enzyme for efficiently reducing peroxides within phospholipid bilayers. Recent data suggest that cancer cells undergoing EMT (dedifferentiation) and those resistant to standard therapy expose a high vulnerability toward ferroptosis. Although recent studies have begun to identify and characterize the metabolic and genetic determinants underlying ferroptosis, many mechanisms that dictate ferroptosis sensitivity remain unknown. Here, we show that low cell density sensitizes primary mammary epithelial and breast cancer cells to ferroptosis induced by GPX4 inhibition, whereas high cell density confers resistance. These effects occur irrespective of oncogenic signaling, cellular phenotype and expression of the fatty acid ligase acyl-CoA synthetase long chain family member 4 (ACSL4). By contrast, we show that a massive accumulation of neutral triacylglycerides (TAG) enriched with polyunsaturated fatty acids (PUFA) is induced at low cell density. In addition, de novo lipogenesis and desaturation pathways were found to be reduced at low cell density, indicative of increased fatty acid uptake. Our study suggests that PUFA-mediated toxicity is limited by the enrichment in TAGs that in turn might pose a vulnerability towards ferroptosis. Conclusively, cell density regulates lipid metabolism of breast epithelial and cancer cells, which results in a ferroptosis-sensitive cell state with the potential to be exploited therapeutically during metastatic dissemination.
HostingRepository	PRIDE
AnnounceDate	2020-11-13
AnnouncementXML	Submission_2020-11-13_08:37:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine von Toerne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-14 02:37:31	ID requested
⏵ 1	2020-11-13 08:37:53	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: triacylglycerides, breast cancer, cell density, ferroptosis, PUFA

Christina Scheel
contact affiliation	Institute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany and Clinic for Dermatology, St. Josef Hospital Bochum, University of Bochum, Gudrunstrasse 56, 44791 Bochum, Germany
contact email	christina.scheel@klinikum-bochum.de
lab head
Christine von Toerne
contact affiliation	Helmholtz Zentrum München
contact email	vontoerne@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/11/PXD016276

PRIDE project URI

• PRIDE
  1. PXD016276
     1. Label: PRIDE project
     2. Name: Cell density-dependent ferroptosis in breast cancer is induced by accumulation of polyunsaturated fatty acid-enriched triacylglycerides