PXD023069

PXD023069 is an original dataset announced via ProteomeXchange.

Title	Integrated lipidomics and proteomics reveal cardiolipin remodelling by upregulation of HADHA and indirectly by ELOVL5 in pancreatic cancer stem cells
Description	Pancreatic cancer stem cells (PCSCs) characterize the pancreatic ductal adenocarcinomas (PDAC) and play a key role in driving their poor outcomes and resistance to targeted therapies. Although advanced proteomics and lipidomics technology facilitates quantitation of intracellular proteins and lipids, little is known about the regulation of signalling and metabolic pathways in PCSCs. Here we shown that PCSCs, derived from different PDAC cell lines, have specific and common proteome and lipidome modulations. PCSCs displayed down-regulation of L-lactate dehydrogenase A chain (LDHA) and, more interestingly, upregulation of trifunctional enzyme subunit alpha (HADHA) which is involved in cardiolipin remodelling. The upregulated proteins of PCSCs were mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics revealed a general increase of FAs 18:1, 20:2, 20:3, and 20:4, which are products of the catalytic activity of fatty acid elongase-5 (ELOVL5) predicted as common active gene of PCSCs. Moreover, in accordance with HADHA upregulation, lipidomics also showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of fatty acid elongation and cardiolipin remodelling in PCSCs, which could therefore represent attractive targets to improve the therapeutic treatments of PDAC
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_15:03:13.465.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-11 04:50:51	ID requested
⏵ 1	2021-09-09 15:03:14	announced

Di Carlo C, Sousa BC, Manfredi M, Brandi J, Dalla Pozza E, Marengo E, Palmieri M, Dando I, Wakelam MJO, Lopez-Clavijo AF, Cecconi D, Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells. Sci Rep, 11(1):13297(2021) [pubmed]

submitter keyword: PDAC, PCSCs, Proteomics, LC-MS/MS

Marcello Manfredi
contact affiliation	Department of Translational Medicine (DiMeT), Center for Translational Research on Autoimmune & Allergic Diseases - CAAD, University of Piemonte Orientale
contact email	marcello.mnfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023069
     1. Label: PRIDE project
     2. Name: Integrated lipidomics and proteomics reveal cardiolipin remodelling by upregulation of HADHA and indirectly by ELOVL5 in pancreatic cancer stem cells