PXD017789

PXD017789 is an original dataset announced via ProteomeXchange.

Title	c-Src functionality controls self-renewal, tumorigenicity and glucose metabolism in breast cancer stem cells
Description	Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells diminished tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of BCSCs (ESA+-CD44+-CD24-) and the tumor-differentiated cells (ESA+-CD44+-CD24+) from MCF7-Tet-On-SrcDN. ESA+-CD44+-CD24- grew in suspension forming mammospheres, and producing tumors in nude mice, while ESA+-CD44+-CD24+ were poorly/non-tumorigenic. Doxycycline-induction of SrcDN inhibited BCSC tumorigenesis, selfrenewal, and stem-cell markers expression. SrcDN significantly inhibited SFE, and stem-cell markers expression in triple-negative breast cancer (TNBC) MDA-MB-231 and SUM159PT cells. Inducible depletion of c-Src caused similar effects in MDA-MB-231 cells. In MCF7-Tet-On-SrcDN derived mammospheres SrcDN-induction inhibited expression, and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, tumorigenicity, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.
HostingRepository	PRIDE
AnnounceDate	2020-07-23
AnnouncementXML	Submission_2020-07-23_01:34:02.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD017789
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sergio Ciordia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iTRAQ4plex; Methylthio; Glu->pyro-Glu; Oxidation; Carbamyl; Acetyl; Gln->pyro-Glu
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-28 08:05:15	ID requested
⏵ 1	2020-07-23 01:34:03	announced

Mayoral-Varo V, Calcabrini A, S, á, nchez-Bail, ó, n MP, Mart, í, nez-Costa Ó H, Gonz, á, lez-P, á, ramos C, Ciordia S, Hardisson D, Arag, ó, n JJ, Fern, á, ndez-Moreno M Á, Mart, í, n-P, é, rez J, c-Src functionality controls self-renewal and glucose metabolism in MCF7 breast cancer stem cells. PLoS One, 15(7):e0235850(2020) [pubmed]

submitter keyword: c-Src, breast cancer stem cells (BCSCs), tumorigenesis, cancer stem cell renewal, glycolysis

Jorge Martín Pérez
contact affiliation	Instituto de Investigaciones Biomédicas A. Sols (CSIC/UAM)
contact email	jmartin@iib.uam.es
lab head
Sergio Ciordia
contact affiliation	Spanish National Center for Biotechnology
contact email	sciordia@cnb.csic.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017789
     1. Label: PRIDE project
     2. Name: c-Src functionality controls self-renewal, tumorigenicity and glucose metabolism in breast cancer stem cells