Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 12% survival rate, highlighting the need for novel therapies. c-MYC overexpression, driven by upstream mutations and amplifications, reprograms tumor metabolism and promotes proliferation, migration and metastasis. This study identifi...

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Detalles Bibliográficos
Autores: García García, Ana, Ferrer Aporta, María, Vallejo Palma, Germán, Giráldez Trujillo, Antonio, Castillo-González, Raquel, Calzón Lozano, David, Mora Perdiguero, Alberto, Muñoz Velasco, Raúl, Colina Castro, Miguel, de Simone Benito, Elena, Torres-Ruiz, Raúl, Rodriguez-Perales, Sandra, Dehairs, Jonas, Swinnen, Johannes V., Garcia-Cañaveras, Juan Carlos, Lahoz, Agustín, Montalvo Quirós, Sandra, del Pozo-Rojas, Carlos, Luque Rioja, Clara, Monroy, Francisco, Herráez-Aguilar, Diego, Alonso Riaño, Marina, Rodríguez Peralto, José Luis, Sánchez-Arévalo Lobo, Víctor Javier
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/7147
Acceso en línea:https://hdl.handle.net/10641/7147
Access Level:acceso abierto
Palabra clave:General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
SDG 3 - Good Health and Well-being
Yes
yes
Descripción
Sumario:Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 12% survival rate, highlighting the need for novel therapies. c-MYC overexpression, driven by upstream mutations and amplifications, reprograms tumor metabolism and promotes proliferation, migration and metastasis. This study identifies ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target. Using PDAC mouse models and cell lines, we show that c-MYC directly upregulates ELOVL6 during tumor progression. Genetic or chemical inhibition of ELOVL6 reduces proliferation and migration by altering fatty acid composition, affecting membrane rigidity, permeability and pinocytosis. These changes increase Abraxane uptake and show a synergistic effect when combined with ELOVL6 inhibition in vitro. In vivo, ELOVL6 interference significantly suppresses tumor growth and improves Abraxane response, prolonging survival. These findings position ELOVL6 as a promising target for improving PDAC treatment outcomes.

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