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PXD011222

PXD011222 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIncreased cholesterol biosynthesis identified as a key feature and a therapeutic target of cancer stem cells as revealed by proteomic comparison of clinical breast cancer tissue and corresponding patient-derived xenografts and mammospheres
DescriptionCancer stem cells (CSCs) comprise a small subpopulation of undifferentiated cancer cells with the ability to self-renew and give rise to the heterogeneous cancer cell lineages that form tumorous masses. Thus, tumor eradication may be greatly improved by specifically targeting CSCs, as they exhibit resistance to conventional therapy. To gain insight into the unique biology of CSCs, we developed patient-derived xenograft (PDX) tumors from ER-negative breast cancer patient tissue from which we isolated mammospheres, a method known to enrich for cells with CSC-properties. An unbiased, comparative global proteomic analysis using label-free mass spectrometry was performed on the patient tumor tissues and corresponding PDX tumors and mammospheres. Good concordance between the proteome profiles of patient tumor tissue and corresponding PDX tumors was observed. However, lower abundance of immune- and extracellular matrix-related proteins and higher abundance of proteins associated with cell-to-cell adhesion including desmosome proteins and β-catenin were observed in PDX versus patient tumors. Interestingly, analysis of proteins elevated in mammospheres vs. PDX tumors identified an enrichment of proteins associated with de novo cholesterol synthesis. The clinical relevance of increased cholesterol biosynthesis protein expression was verified in a large gene expression data set of clinical breast cancers showing correlation with shorter relapse-free survival. RNA interference and chemical inhibition of the cholesterol biosynthesis pathway reduced mammosphere formation and growth of CSCs derived from PDX tumors and cancer cell lines. Our findings identify the cholesterol biosynthesis pathway as central for CSC growth and a potential therapeutic target for CSC as well as providing an additional mechanistic explanation for the observed benefit of statins in breast cancer treatment.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:49:07.955.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBrian Hood
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListcarbamoylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-09-28 07:48:30ID requested
12019-07-02 00:11:09announced
22024-10-22 04:49:16announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.celrep.2019.05.104;
Ehmsen S, Pedersen MH, Wang G, Terp MG, Arslanagic A, Hood BL, Conrads TP, Leth-Larsen R, Ditzel HJ, Increased Cholesterol Biosynthesis Is a Key Characteristic of Breast Cancer Stem Cells Influencing Patient Outcome. Cell Rep, 27(13):3927-3938.e6(2019) [pubmed]
Keyword List
submitter keyword: FFPE Tissue,Breast Cancer Proteomics
Contact List
Henrik J. Ditzel
contact affiliationDepartment of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark
contact emailhditzel@health.sdu.dk
lab head
Brian Hood
contact affiliationWomen's Health Integrated Research Center
contact emailhoodb@whirc.org
dataset submitter
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Dataset FTP location
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PRIDE project URI
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