Lineage-restricted regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity.
dc.contributor.author | Vivas-García, Yurena | |
dc.contributor.author | Falletta, P | |
dc.contributor.author | Liebing, J | |
dc.contributor.author | Louphrasitthiphol, P | |
dc.contributor.author | Feng, Y | |
dc.contributor.author | Chauhan, J | |
dc.contributor.author | Scott, DA | |
dc.contributor.author | Glodde, N | |
dc.contributor.author | Chocarro-Calvo, A | |
dc.contributor.author | Bonham, S | |
dc.contributor.author | Osterman, A | |
dc.contributor.author | Fischer, R | |
dc.contributor.author | Ronai, Z | |
dc.contributor.author | García-Jiménez, C | |
dc.contributor.author | Hölzel, M | |
dc.contributor.author | Goding, CR | |
dc.date.accessioned | 2024-01-26T12:41:27Z | |
dc.date.available | 2024-01-26T12:41:27Z | |
dc.date.issued | 2020-01-02 | |
dc.description.abstract | Phenotypic and metabolic heterogeneity within tumors is a major barrier to effective cancer therapy. How metabolism is implicated in specific phenotypes and whether lineage-restricted mechanisms control key metabolic vulnerabilities remain poorly understood. In melanoma, downregulation of the lineage addiction oncogene microphthalmia-associated transcription factor (MITF) is a hallmark of the proliferative-to-invasive phenotype switch, although how MITF promotes proliferation and suppresses invasion is poorly defined. Here, we show that MITF is a lineage-restricted activator of the key lipogenic enzyme stearoyl-CoA desaturase (SCD) and that SCD is required for MITFHigh melanoma cell proliferation. By contrast MITFLow cells are insensitive to SCD inhibition. Significantly, the MITF-SCD axis suppresses metastasis, inflammatory signaling, and an ATF4-mediated feedback loop that maintains de-differentiation. Our results reveal that MITF is a lineage-specific regulator of metabolic reprogramming, whereby fatty acid composition is a driver of melanoma phenotype switching, and highlight that cell phenotype dictates the response to drugs targeting lipid metabolism. | es |
dc.identifier.citation | Mol Cell . 2020 Jan 2;77(1):120-137.e9 | es |
dc.identifier.doi | 10.1016/j.molcel.2019.10.014 | es |
dc.identifier.issn | 1097-2765 | |
dc.identifier.uri | https://hdl.handle.net/10115/29028 | |
dc.language.iso | eng | es |
dc.publisher | Mol Cell | es |
dc.rights.accessRights | info:eu-repo/semantics/restrictedAccess | es |
dc.subject | ATF4 | es |
dc.subject | MITF | es |
dc.subject | fatty acid saturation | es |
dc.subject | melanoma | es |
dc.subject | metastatic dissemination | es |
dc.subject | phenotype switching | es |
dc.subject | stearoyl CoA desaturase | es |
dc.title | Lineage-restricted regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity. | es |
dc.type | info:eu-repo/semantics/article | es |
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