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A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells

Rivas Serna, IM; Romito, I; Maugeri, A; Lo Re, O; Giallongo, S; Mazzoccoli, G; Oben, JA; ... Vinciguerra, M; + view all (2020) A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells. International Journal of Molecular Sciences , 21 (22) , Article 8452. 10.3390/ijms21228452. Green open access

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Abstract

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.

Type: Article
Title: A Lipidomic Signature Complements Stemness Features Acquisition in Liver Cancer Cells
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms21228452
Publisher version: http://dx.doi.org/10.3390/ijms21228452
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Keywords: FAK, HCC, cancer stem cells, macroH2A1, stemness
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10117444
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