Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis.
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| Autori principali: | , , , , , , , , , , , , , , , , , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
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Science advances
2024
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| author | More, Sanket Bonnereau, Julie Wouters, David Spotbeen, Xander Karras, Panagiotis Rizzollo, Francesca Killian, Theo Venken, Tom Naulaerts, Stefan Vervoort, Ellen Ganne, Maarten Nittner, David Verhoeven, Jelle Bechter, Oliver Bosisio, Francesca Lambrechts, Diether Sifrim, Alejandro Stockwell, Brent R Swinnen, Johannes V Marine, Jean Christophe Agostinis, Patrizia |
| author_facet | More, Sanket Bonnereau, Julie Wouters, David Spotbeen, Xander Karras, Panagiotis Rizzollo, Francesca Killian, Theo Venken, Tom Naulaerts, Stefan Vervoort, Ellen Ganne, Maarten Nittner, David Verhoeven, Jelle Bechter, Oliver Bosisio, Francesca Lambrechts, Diether Sifrim, Alejandro Stockwell, Brent R Swinnen, Johannes V Marine, Jean Christophe Agostinis, Patrizia More, Sanket Bonnereau, Julie Wouters, David Spotbeen, Xander Karras, Panagiotis Rizzollo, Francesca Killian, Theo Venken, Tom Naulaerts, Stefan Vervoort, Ellen Ganne, Maarten Nittner, David Verhoeven, Jelle Bechter, Oliver Bosisio, Francesca Lambrechts, Diether Sifrim, Alejandro Stockwell, Brent R Swinnen, Johannes V Marine, Jean Christophe Agostinis, Patrizia |
| collection | PubMed - marine biology |
| contents | Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis. More, Sanket Bonnereau, Julie Wouters, David Spotbeen, Xander Karras, Panagiotis Rizzollo, Francesca Killian, Theo Venken, Tom Naulaerts, Stefan Vervoort, Ellen Ganne, Maarten Nittner, David Verhoeven, Jelle Bechter, Oliver Bosisio, Francesca Lambrechts, Diether Sifrim, Alejandro Stockwell, Brent R Swinnen, Johannes V Marine, Jean Christophe Agostinis, Patrizia Ferroptosis Melanoma Humans Apolipoproteins E Cell Line, Tumor Mice Animals Gene Expression Regulation, Neoplastic Phospholipid Hydroperoxide Glutathione Peroxidase A major therapeutic barrier in melanoma is the coexistence of diverse cellular states marked by distinct metabolic traits. Transitioning from a proliferative to an invasive melanoma phenotype is coupled with increased ferroptosis vulnerability. However, the regulatory circuits controlling ferroptosis susceptibility across melanoma cell states are unknown. In this work, we identified Apolipoprotein E () as the top lipid-metabolism gene segregating the melanoma MITF/AXL proliferative/ferroptosis-resistant from MITF/AXL invasive/ferroptosis-sensitive state. Mechanistically, ApoE secreted by the MITF/AXL cells protects the invasive phenotype from ferroptosis-inducing agents by reducing the content of peroxidation-prone polyunsaturated fatty acids and boosting GPX4 levels both in vitro and in vivo. Whole-exome sequencing indicates that expression in patients with melanoma is associated with resistance to ferroptosis, regardless of germline status. In aggregate, we found a ferroptosis-resistance mechanism between melanoma cell states relying on secreted ApoE and expression as a potential biomarker for poor ferroptosis response in melanoma. |
| format | Artículo científico |
| id | pubmed_39413195 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | Science advances |
| record_format | pubmed |
| spellingShingle | Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis. More, Sanket Bonnereau, Julie Wouters, David Spotbeen, Xander Karras, Panagiotis Rizzollo, Francesca Killian, Theo Venken, Tom Naulaerts, Stefan Vervoort, Ellen Ganne, Maarten Nittner, David Verhoeven, Jelle Bechter, Oliver Bosisio, Francesca Lambrechts, Diether Sifrim, Alejandro Stockwell, Brent R Swinnen, Johannes V Marine, Jean Christophe Agostinis, Patrizia Ferroptosis Melanoma Humans Apolipoproteins E Cell Line, Tumor Mice Animals Gene Expression Regulation, Neoplastic Phospholipid Hydroperoxide Glutathione Peroxidase Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis. More, Sanket Bonnereau, Julie Wouters, David Spotbeen, Xander Karras, Panagiotis Rizzollo, Francesca Killian, Theo Venken, Tom Naulaerts, Stefan Vervoort, Ellen Ganne, Maarten Nittner, David Verhoeven, Jelle Bechter, Oliver Bosisio, Francesca Lambrechts, Diether Sifrim, Alejandro Stockwell, Brent R Swinnen, Johannes V Marine, Jean Christophe Agostinis, Patrizia Ferroptosis Melanoma Humans Apolipoproteins E Cell Line, Tumor Mice Animals Gene Expression Regulation, Neoplastic Phospholipid Hydroperoxide Glutathione Peroxidase A major therapeutic barrier in melanoma is the coexistence of diverse cellular states marked by distinct metabolic traits. Transitioning from a proliferative to an invasive melanoma phenotype is coupled with increased ferroptosis vulnerability. However, the regulatory circuits controlling ferroptosis susceptibility across melanoma cell states are unknown. In this work, we identified Apolipoprotein E () as the top lipid-metabolism gene segregating the melanoma MITF/AXL proliferative/ferroptosis-resistant from MITF/AXL invasive/ferroptosis-sensitive state. Mechanistically, ApoE secreted by the MITF/AXL cells protects the invasive phenotype from ferroptosis-inducing agents by reducing the content of peroxidation-prone polyunsaturated fatty acids and boosting GPX4 levels both in vitro and in vivo. Whole-exome sequencing indicates that expression in patients with melanoma is associated with resistance to ferroptosis, regardless of germline status. In aggregate, we found a ferroptosis-resistance mechanism between melanoma cell states relying on secreted ApoE and expression as a potential biomarker for poor ferroptosis response in melanoma. |
| title | Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis. |
| topic | Ferroptosis Melanoma Humans Apolipoproteins E Cell Line, Tumor Mice Animals Gene Expression Regulation, Neoplastic Phospholipid Hydroperoxide Glutathione Peroxidase |
| url | https://pubmed.ncbi.nlm.nih.gov/39413195/ |