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Int. J. Mol. Sci. 2017, 18(6), 1271;

Lipid Storage and Autophagy in Melanoma Cancer Cells

Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome 00161, Italy
Department of Oncology and Molecular Medicine Istituto Superiore di Sanità, ISS, Rome 00161, Italy
Istituto Dermopatico dell’Immacolata IDI-IRCCS, Rome 00167, Italy
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 16 May 2017 / Revised: 12 June 2017 / Accepted: 13 June 2017 / Published: 15 June 2017
(This article belongs to the Special Issue Stem Cell Research)
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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. View Full-Text
Keywords: stem cells; autophagy; lipids; melanoma stem cells; autophagy; lipids; melanoma

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Giampietri, C.; Petrungaro, S.; Cordella, M.; Tabolacci, C.; Tomaipitinca, L.; Facchiano, A.; Eramo, A.; Filippini, A.; Facchiano, F.; Ziparo, E. Lipid Storage and Autophagy in Melanoma Cancer Cells. Int. J. Mol. Sci. 2017, 18, 1271.

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