A lipidomic signature complements stemness features acquisition in liver cancer cells

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number8452
Pages (from-to)1-18
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume21
Issue number22
DOIs
Publication statusPublished - Nov 2 2020

Keywords

  • Cancer stem cells
  • FAK
  • HCC
  • MacroH2A1
  • Stemness

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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