A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells
Lipid catabolism and anabolism changes play a role in stemness acquisition by cancer cells, and cancer stem cells (CSCs) are particularly dependent on the activity of the enzymes involved in these processes. Lipidomic changes could play a role in CSCs’ ability to cause disease relapse and chemoresis...
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doaj-3201d22e5ff445f08894bad3baf700bd2020-11-25T04:00:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218452845210.3390/ijms21228452A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer CellsIrma Magaly Rivas Serna0Ilaria Romito1Andrea Maugeri2Oriana Lo Re3Sebastiano Giallongo4Gianluigi Mazzoccoli5Jude A. Oben6Giovanni Li Volti7Tommaso Mazza8Anna Alisi9Manlio Vinciguerra10International Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech RepublicResearch Area for Multifactorial Diseases, Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyDepartment of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95123 Catania, ItalyInternational Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech RepublicInternational Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech RepublicDepartment of Medical Sciences and Chronobiology Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyInstitute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London NW32PF, UKDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95131 Catania, ItalyBioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, ItalyResearch Area for Multifactorial Diseases, Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyInternational Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech RepublicLipid catabolism and anabolism changes play a role in stemness acquisition by cancer cells, and cancer stem cells (CSCs) are particularly dependent on the activity of the enzymes involved in these processes. Lipidomic changes could play a role in CSCs’ ability to cause disease relapse and chemoresistance. The exploration of lipid composition and metabolism changes in CSCs in the context of hepatocellular cancer (HCC) is still incomplete and their lipidomic scenario continues to be elusive. We aimed to evaluate through high-throughput mass spectrometry (MS)-based lipidomics the levels of the members of the six major classes of sphingolipids and phospholipids in two HCC cell lines (HepG2 and Huh-7) silenced for the expression of histone variant macroH2A1 (favoring stemness acquisition), or silenced for the expression of focal adhesion tyrosine kinase (FAK) (hindering aggressiveness and stemness). Transcriptomic changes were evaluated by RNA sequencing as well. We found definite lipidomic and transcriptomic changes in the HCC lines upon knockdown (KD) of macroH2A1 or FAK, in line with the acquisition or loss of stemness features. In particular, macroH2A1 KD increased total sphingomyelin (SM) levels and decreased total lysophosphatidylcholine (LPC) levels, while FAK KD decreased total phosphatidylcholine (PC) levels. In conclusion, in HCC cell lines knocked down for specific signaling/epigenetic processes driving opposite stemness potential, we defined a lipidomic signature that hallmarks hepatic CSCs to be exploited for therapeutic strategies.https://www.mdpi.com/1422-0067/21/22/8452macroH2A1FAKHCCstemnesscancer stem cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Irma Magaly Rivas Serna Ilaria Romito Andrea Maugeri Oriana Lo Re Sebastiano Giallongo Gianluigi Mazzoccoli Jude A. Oben Giovanni Li Volti Tommaso Mazza Anna Alisi Manlio Vinciguerra |
spellingShingle |
Irma Magaly Rivas Serna Ilaria Romito Andrea Maugeri Oriana Lo Re Sebastiano Giallongo Gianluigi Mazzoccoli Jude A. Oben Giovanni Li Volti Tommaso Mazza Anna Alisi Manlio Vinciguerra A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells International Journal of Molecular Sciences macroH2A1 FAK HCC stemness cancer stem cells |
author_facet |
Irma Magaly Rivas Serna Ilaria Romito Andrea Maugeri Oriana Lo Re Sebastiano Giallongo Gianluigi Mazzoccoli Jude A. Oben Giovanni Li Volti Tommaso Mazza Anna Alisi Manlio Vinciguerra |
author_sort |
Irma Magaly Rivas Serna |
title |
A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells |
title_short |
A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells |
title_full |
A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells |
title_fullStr |
A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells |
title_full_unstemmed |
A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells |
title_sort |
lipidomic signature complements stemness features acquisition in liver cancer cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-11-01 |
description |
Lipid catabolism and anabolism changes play a role in stemness acquisition by cancer cells, and cancer stem cells (CSCs) are particularly dependent on the activity of the enzymes involved in these processes. Lipidomic changes could play a role in CSCs’ ability to cause disease relapse and chemoresistance. The exploration of lipid composition and metabolism changes in CSCs in the context of hepatocellular cancer (HCC) is still incomplete and their lipidomic scenario continues to be elusive. We aimed to evaluate through high-throughput mass spectrometry (MS)-based lipidomics the levels of the members of the six major classes of sphingolipids and phospholipids in two HCC cell lines (HepG2 and Huh-7) silenced for the expression of histone variant macroH2A1 (favoring stemness acquisition), or silenced for the expression of focal adhesion tyrosine kinase (FAK) (hindering aggressiveness and stemness). Transcriptomic changes were evaluated by RNA sequencing as well. We found definite lipidomic and transcriptomic changes in the HCC lines upon knockdown (KD) of macroH2A1 or FAK, in line with the acquisition or loss of stemness features. In particular, macroH2A1 KD increased total sphingomyelin (SM) levels and decreased total lysophosphatidylcholine (LPC) levels, while FAK KD decreased total phosphatidylcholine (PC) levels. In conclusion, in HCC cell lines knocked down for specific signaling/epigenetic processes driving opposite stemness potential, we defined a lipidomic signature that hallmarks hepatic CSCs to be exploited for therapeutic strategies. |
topic |
macroH2A1 FAK HCC stemness cancer stem cells |
url |
https://www.mdpi.com/1422-0067/21/22/8452 |
work_keys_str_mv |
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