The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells
Stimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and hum...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/1099 |
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| author | Giorgia Cardinali Daniela Kovacs Sarah Mosca Barbara Bellei Enrica Flori Aldo Morrone Anna Maria Mileo Vittoria Maresca |
| author_facet | Giorgia Cardinali Daniela Kovacs Sarah Mosca Barbara Bellei Enrica Flori Aldo Morrone Anna Maria Mileo Vittoria Maresca |
| author_sort | Giorgia Cardinali |
| collection | DOAJ |
| description | Stimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and human melanoma cells. Treatment with αMSH plus LY294002 altered cortical actin architecture. Given that cytoskeleton integrity requires energy, we next evaluated ATP levels and we observed a drop in ATP after exposure to αMSH plus LY294002. To evaluate if the αMSH-activated PI3K pathway could modulate energy metabolism, we focused on glucose uptake by analyzing the expression of the Glut-1 glucose translocator. Compared with cells treated with αMSH alone, those exposed to combined treatment showed a reduction of Glut-1 on the plasma membrane. This metabolic alteration was associated with changes in mitochondrial mass. A significant decrease of the cell migratory potential was also observed. We demonstrated that the αMSH-dependent PI3K pathway acts as a regulator of energy metabolism via glucose uptake, influencing the actin cytoskeleton, which is involved in melanosome release and cell motility. Hence, these results could constitute the basis for innovative therapeutical strategies. |
| first_indexed | 2024-03-11T05:40:02Z |
| format | Article |
| id | doaj.art-993c6cb220b14dc9b612695a2a85ae7c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:40:02Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-993c6cb220b14dc9b612695a2a85ae7c2023-11-17T16:29:17ZengMDPI AGCells2073-44092023-04-01127109910.3390/cells12071099The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma CellsGiorgia Cardinali0Daniela Kovacs1Sarah Mosca2Barbara Bellei3Enrica Flori4Aldo Morrone5Anna Maria Mileo6Vittoria Maresca7Laboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyLaboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyLaboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyLaboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyLaboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyLaboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyTumor Immunology and Immunotherapy Unit, Department of Research Advanced Diagnostic and Technological Innovation, Regina Elena National Cancer Institute, IRCCS, 00144 Rome, ItalyLaboratory of Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, ItalyStimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and human melanoma cells. Treatment with αMSH plus LY294002 altered cortical actin architecture. Given that cytoskeleton integrity requires energy, we next evaluated ATP levels and we observed a drop in ATP after exposure to αMSH plus LY294002. To evaluate if the αMSH-activated PI3K pathway could modulate energy metabolism, we focused on glucose uptake by analyzing the expression of the Glut-1 glucose translocator. Compared with cells treated with αMSH alone, those exposed to combined treatment showed a reduction of Glut-1 on the plasma membrane. This metabolic alteration was associated with changes in mitochondrial mass. A significant decrease of the cell migratory potential was also observed. We demonstrated that the αMSH-dependent PI3K pathway acts as a regulator of energy metabolism via glucose uptake, influencing the actin cytoskeleton, which is involved in melanosome release and cell motility. Hence, these results could constitute the basis for innovative therapeutical strategies.https://www.mdpi.com/2073-4409/12/7/1099melanomaPI3K pathwayαMSHglucose uptakeenergy metabolism |
| spellingShingle | Giorgia Cardinali Daniela Kovacs Sarah Mosca Barbara Bellei Enrica Flori Aldo Morrone Anna Maria Mileo Vittoria Maresca The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells Cells melanoma PI3K pathway αMSH glucose uptake energy metabolism |
| title | The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells |
| title_full | The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells |
| title_fullStr | The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells |
| title_full_unstemmed | The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells |
| title_short | The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells |
| title_sort | αmsh dependent pi3k pathway supports energy metabolism via glucose uptake in melanoma cells |
| topic | melanoma PI3K pathway αMSH glucose uptake energy metabolism |
| url | https://www.mdpi.com/2073-4409/12/7/1099 |
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