PXD006216

PXD006216 is an original dataset announced via ProteomeXchange.

Title	Chemotherapy-induced cellular senescence is characterized by aberrant lipid regulation and lipid peroxidation
Description	As normal cells approach their proliferative limit, they arrest to undergo replicative senescence, displaying large cell size, flat morphology and activation of senescence-associated beta-galactosidase (SA-b-Gal). A subset of normal or tumor cells exposed in vitro or in vivo to chemotherapy agents such as etoposide perform a related response with a similar cellular phenotype dubbed therapy-induced senescence (TIS). High cellular heterogeneity in samples including TIS cells can impede confident determination of senescence-specific factors, frustrating discovery of markers and targets for functional analysis. As a TIS study model, we treated murine melanoma cells with the chemotherapeutic etoposide, applied a live-cell fluorescent SA-b-Gal senescence assay, and utilized fluorescence-activated cell sorting (FACS) to enrich TIS cells. Enriched senescent cell samples were subjected to mass spectrometry and label-free quantitative proteomics analysis, alongside proliferating and quiescent cell samples. Systems biology analysis revealed that senescent cells overexpress proteins and pathways regulating glycolipid processing, lipid metabolism, and lipid peroxidation. Senescence-associated activation of numerous glycosidases was observed, along with elevated cell surface expression of several major lipid regulatory proteins. Senescent cells were found to contain abundant lipid droplets and to import various types of extracellular lipids in correlation with extent of SA-b-Gal expression, and tumor cells were observed to spontaneously senesce in the presence of excess ceramide or triglycerides. Redox-induced lipid peroxidation, resulting in accumulation of cellular reactive aldehydes and consequent expression of aldehyde detoxification enzymes, was observed to be a key feature of TIS induced by three DNA-damaging chemotherapeutics.
HostingRepository	PRIDE
AnnounceDate	2017-11-06
AnnouncementXML	Submission_2017-11-06_01:00:22.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD006216
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Donald Wolfgeher
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	HNE; Ammonia-loss; Deamidated; Formyl; Dehydrated; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-30 03:14:05	ID requested
⏵ 1	2017-11-06 01:00:23	announced

Flor AC, Wolfgeher D, Wu D, Kron SJ, A signature of enhanced lipid metabolism, lipid peroxidation and aldehyde stress in therapy-induced senescence. Cell Death Discov, 3():17075(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Q-Exactive, Maxquant LFQ, Quant Proteomics, Chemotherapy-Induced Senescence, Mus, Lipid Peroxidation

Stephen J Kron
contact affiliation	University of Chicago. Biological Sciences Division, Molecular Genetics & Cell Biology
contact email	skron@uchicago.edu
lab head
Donald Wolfgeher
contact affiliation	University of Chicago
contact email	donw@uchicago.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006216
     1. Label: PRIDE project
     2. Name: Chemotherapy-induced cellular senescence is characterized by aberrant lipid regulation and lipid peroxidation