Lipid Storage and Autophagy in Melanoma Cancer Cells

• Published in: International journal of molecular sciences 2017-06, Vol.18 (6), p.1271
• Main Authors: Giampietri, Claudia, Petrungaro, Simonetta, Cordella, Martina, Tabolacci, Claudio, Tomaipitinca, Luana, Facchiano, Antonio, Eramo, Adriana, Filippini, Antonio, Facchiano, Francesco, Ziparo, Elio
• Format: Article
• Language: English
• Subjects: AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Autophagy; Cancer; Cell Differentiation; Colorectal cancer; Droplets; Enzymes; Fatty acids; Genotype & phenotype; Humans; Kinases; Lipid Metabolism; Lipids; Localization; Melanoma; Melanoma - metabolism; Melanoma - pathology; Metabolism; Metastasis; Microtubule-associated protein 1; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Peroxisome proliferator-activated receptors; Phenotypes; Phosphorylation; PPAR gamma - metabolism; Proteins; Rapamycin; Skin cancer; Stem cells; Sterol Regulatory Element Binding Protein 1 - metabolism; Sterol regulatory element-binding protein; Sterols; Storage; TOR protein; TOR Serine-Threonine Kinases - metabolism; Triglycerides; Tumor Cells, Cultured; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18061271

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.