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

Abstract 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...

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Autores principales:	Claudia Di Carlo, Bebiana C. Sousa, Marcello Manfredi, Jessica Brandi, Elisa Dalla Pozza, Emilio Marengo, Marta Palmieri, Ilaria Dando, Michael J. O. Wakelam, Andrea F. Lopez-Clavijo, Daniela Cecconi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ecf05d9ceac409bb21256e8799d63d9
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spelling	oai:doaj.org-article:7ecf05d9ceac409bb21256e8799d63d92021-12-02T16:07:04ZIntegrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells10.1038/s41598-021-92752-52045-2322https://doaj.org/article/7ecf05d9ceac409bb21256e8799d63d92021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92752-5https://doaj.org/toc/2045-2322Abstract 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.Claudia Di CarloBebiana C. SousaMarcello ManfrediJessica BrandiElisa Dalla PozzaEmilio MarengoMarta PalmieriIlaria DandoMichael J. O. WakelamAndrea F. Lopez-ClavijoDaniela CecconiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Di Carlo Bebiana C. Sousa Marcello Manfredi Jessica Brandi Elisa Dalla Pozza Emilio Marengo Marta Palmieri Ilaria Dando Michael J. O. Wakelam Andrea F. Lopez-Clavijo Daniela Cecconi Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
description	Abstract 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.
format	article
author	Claudia Di Carlo Bebiana C. Sousa Marcello Manfredi Jessica Brandi Elisa Dalla Pozza Emilio Marengo Marta Palmieri Ilaria Dando Michael J. O. Wakelam Andrea F. Lopez-Clavijo Daniela Cecconi
author_facet	Claudia Di Carlo Bebiana C. Sousa Marcello Manfredi Jessica Brandi Elisa Dalla Pozza Emilio Marengo Marta Palmieri Ilaria Dando Michael J. O. Wakelam Andrea F. Lopez-Clavijo Daniela Cecconi
author_sort	Claudia Di Carlo
title	Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
title_short	Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
title_full	Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
title_fullStr	Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
title_full_unstemmed	Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells
title_sort	integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of hadha and long chain fatty acids in pancreatic cancer stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7ecf05d9ceac409bb21256e8799d63d9
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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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