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 journalArticle

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 differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-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
JournalInternational Journal of Molecular Sciences
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 15 2017

Keywords

  • AMP-Activated Protein Kinases/metabolism
  • Autophagy
  • Cell Differentiation
  • Humans
  • Lipid Metabolism
  • Melanoma/metabolism
  • Neoplastic Stem Cells/metabolism
  • PPAR gamma/metabolism
  • Phosphorylation
  • Sterol Regulatory Element Binding Protein 1/metabolism
  • TOR Serine-Threonine Kinases/metabolism
  • Tumor Cells, Cultured

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  • Cite this

    Giampietri, C., Petrungaro, S., Cordella, M., Tabolacci, C., Tomaipitinca, L., Facchiano, A., Eramo, A., Filippini, A., Facchiano, F., & Ziparo, E. (2017). Lipid Storage and Autophagy in Melanoma Cancer Cells. International Journal of Molecular Sciences, 18(6). https://doi.org/10.3390/ijms18061271