Integrated lipidomics and proteomics reveal cardiolipin remodelling by upregulation of HADHA and indirectly by ELOVL5 in pancreatic cancer stem cells

ABSTRACT: 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

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Pancreatic Ductal Adenocarcinoma

SUBMITTER: Marcello Manfredi  

LAB HEAD: Marcello Manfredi

PROVIDER: PXD023069 | Pride | 2021-09-09

REPOSITORIES: Pride