PXD011222

PXD011222 is an original dataset announced via ProteomeXchange.

Title	Increased 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
Description	Cancer 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:49:07.955.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brian Hood
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-09-28 07:48:30	ID requested
1	2019-07-02 00:11:09	announced
⏵ 2	2024-10-22 04:49:16	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: FFPE Tissue,Breast Cancer Proteomics

Henrik J. Ditzel
contact affiliation	Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark
contact email	hditzel@health.sdu.dk
lab head
Brian Hood
contact affiliation	Women's Health Integrated Research Center
contact email	hoodb@whirc.org
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/2019/07/PXD011222

PRIDE project URI

• PRIDE
  1. PXD011222
     1. Label: PRIDE project
     2. Name: Increased 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