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Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells.

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Di Carlo, Claudia 
Sousa, Bebiana C 
Manfredi, Marcello 
Brandi, Jessica 
Dalla Pozza, Elisa 


Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics 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 FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.



Carcinoma, Pancreatic Ductal, Cardiolipins, Humans, Lipid Metabolism, Lipidomics, Mitochondrial Trifunctional Protein, alpha Subunit, Neoplastic Stem Cells, Pancreatic Neoplasms, Proteomics, Up-Regulation

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Springer Science and Business Media LLC