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

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

doi:10.1038/s41598-021-92752-5

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

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

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
Numero di articolo	13297
Rivista	Scientific Reports
Volume	11
Numero di pubblicazione	1
DOI	https://doi.org/10.1038/s41598-021-92752-5
Stato di pubblicazione	Pubblicato - dic 2021

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Di Carlo, C., Sousa, B. C., Manfredi, M., Brandi, J., Dalla Pozza, E., Marengo, E., Palmieri, M., Dando, I., Wakelam, M. J. O., Lopez-Clavijo, A. F., & Cecconi, D. (2021). Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells. Scientific Reports, 11(1), Articolo 13297. https://doi.org/10.1038/s41598-021-92752-5

@article{18742b34dbd94190a70169c13bc8515d,

title = "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 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.",

author = "{Di Carlo}, Claudia and Sousa, {Bebiana C.} and Marcello Manfredi and Jessica Brandi and {Dalla Pozza}, Elisa and Emilio Marengo and Marta Palmieri and Ilaria Dando and Wakelam, {Michael J.O.} and Lopez-Clavijo, {Andrea F.} and Daniela Cecconi",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41598-021-92752-5",

language = "English",

volume = "11",

journal = "Scientific Reports",

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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 2021, 'Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells', Scientific Reports, vol. 11, n. 1, 13297. https://doi.org/10.1038/s41598-021-92752-5

TY - JOUR

T1 - Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells

AU - Di Carlo, Claudia

AU - Sousa, Bebiana C.

AU - Manfredi, Marcello

AU - Brandi, Jessica

AU - Dalla Pozza, Elisa

AU - Marengo, Emilio

AU - Palmieri, Marta

AU - Dando, Ilaria

AU - Wakelam, Michael J.O.

AU - Lopez-Clavijo, Andrea F.

AU - Cecconi, Daniela

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

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JO - Scientific Reports

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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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