Lipid storage and autophagy in melanoma cancer cells

Claudia Giampietri, Simonetta Petrungaro, Martina Cordella, Claudio Tabolacci, Luana Tomaipitinca, Antonio Facchiano, Adriana Eramo, Antonio Filippini, Francesco Facchiano, Elio Ziparo

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiatingmelanosphere-derived cells. Increased lipid uptakewas found inmelanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ(PPAR-γ). An inverse relation between lipid-storing phenotype and autophagy was also found, since microtubule-associated protein 1A/1B-Light Chain 3 (LC3) lipidation is reduced in melanosphere-derived CSC. To investigate upstream autophagy regulators, Phospho-AMP activated Protein Kinase (P-AMPK) and Phospho-mammalian Target of Rapamycin (P-mTOR) were analyzed; lower P-AMPK and higher P-mTOR expression in melanosphere-derived CSC were found, thus explaining, at least in part, their lower autophagic activity. In addition, co-localization of LC3-stained autophagosome spots and perilipin-stained lipid droplets was demonstrated mainly in differentiating melanosphere-derived cells, further supporting the role of autophagy in lipid droplets clearance. The present manuscript demonstrates an inverse relationship between lipid-storing phenotype and melanoma stem cells differentiation, providing novel indications involving autophagy in melanoma stem cells biology.

Original languageEnglish
Article number1271
JournalInternational Journal of Molecular Sciences
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 15 2017

Keywords

  • Autophagy
  • Lipids
  • Melanoma
  • Stem cells

ASJC Scopus subject areas

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

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