PMID- 33182805 OWN - NLM STAT- MEDLINE DCOM- 20210505 LR - 20210505 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 22 DP - 2020 Nov 10 TI - A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells. LID - 10.3390/ijms21228452 [doi] LID - 8452 AB - 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. FAU - Rivas Serna, Irma Magaly AU - Rivas Serna IM AD - International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. FAU - Romito, Ilaria AU - Romito I AD - Research Area for Multifactorial Diseases, Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesu Children's Hospital, IRCCS, 00165 Rome, Italy. FAU - Maugeri, Andrea AU - Maugeri A AD - Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, 95123 Catania, Italy. FAU - Lo Re, Oriana AU - Lo Re O AD - International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. FAU - Giallongo, Sebastiano AU - Giallongo S AD - International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. AD - Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic. FAU - Mazzoccoli, Gianluigi AU - Mazzoccoli G AUID- ORCID: 0000-0003-3535-7635 AD - Department of Medical Sciences and Chronobiology Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy. FAU - Oben, Jude A AU - Oben JA AD - Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London NW32PF, UK. FAU - Li Volti, Giovanni AU - Li Volti G AUID- ORCID: 0000-0002-8678-2183 AD - Department of Biomedical and Biotechnological Sciences, University of Catania, 95131 Catania, Italy. FAU - Mazza, Tommaso AU - Mazza T AUID- ORCID: 0000-0003-0434-8533 AD - Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy. FAU - Alisi, Anna AU - Alisi A AUID- ORCID: 0000-0001-7241-6329 AD - Research Area for Multifactorial Diseases, Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesu Children's Hospital, IRCCS, 00165 Rome, Italy. FAU - Vinciguerra, Manlio AU - Vinciguerra M AUID- ORCID: 0000-0002-1768-3894 AD - International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic. AD - Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), London NW32PF, UK. AD - ERA Chair in Translational Stem Cell Biology, Medical University of Varna, 9002 Varna, Bulgaria. LA - eng GR - CZ.02.1.01/0.0/0.0/15_003/0000492/European Research Development Fund/ GR - NV18-03-00058/Ministry of Health of the Czech Republic/ PT - Journal Article DEP - 20201110 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers, Tumor) RN - 0 (Histones) RN - 0 (Lysophosphatidylcholines) RN - 0 (MACROH2A1 protein, human) RN - 0 (Phosphatidylcholines) RN - 0 (Sphingomyelins) RN - EC 2.7.10.2 (Focal Adhesion Kinase 1) RN - EC 2.7.10.2 (PTK2 protein, human) SB - IM MH - Biomarkers, Tumor/genetics/metabolism MH - Carcinoma, Hepatocellular/genetics/*metabolism/*pathology MH - Cell Line, Tumor MH - Focal Adhesion Kinase 1/antagonists & inhibitors/deficiency/genetics MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Hep G2 Cells MH - Histones/antagonists & inhibitors/deficiency/genetics MH - Humans MH - *Lipid Metabolism/genetics MH - Lipidomics MH - Liver Neoplasms/genetics/*metabolism/*pathology MH - Lysophosphatidylcholines/metabolism MH - Neoplastic Stem Cells/*metabolism/*pathology MH - Phosphatidylcholines/metabolism MH - RNA-Seq MH - Sphingomyelins/metabolism PMC - PMC7709039 OTO - NOTNLM OT - FAK OT - HCC OT - cancer stem cells OT - macroH2A1 OT - stemness COIS- The authors declare no competing financial interests. EDAT- 2020/11/14 06:00 MHDA- 2021/05/06 06:00 PMCR- 2020/11/01 CRDT- 2020/11/13 01:04 PHST- 2020/10/20 00:00 [received] PHST- 2020/11/06 00:00 [revised] PHST- 2020/11/09 00:00 [accepted] PHST- 2020/11/13 01:04 [entrez] PHST- 2020/11/14 06:00 [pubmed] PHST- 2021/05/06 06:00 [medline] PHST- 2020/11/01 00:00 [pmc-release] AID - ijms21228452 [pii] AID - ijms-21-08452 [pii] AID - 10.3390/ijms21228452 [doi] PST - epublish SO - Int J Mol Sci. 2020 Nov 10;21(22):8452. doi: 10.3390/ijms21228452.