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

Ana García García, María Ferrer Aporta, Germán Vallejo Palma, Antonio Giráldez Trujillo, Raquel Castillo-González, David Calzón Lozano, Alberto Mora Perdiguero, Raúl Muñoz Velasco, Miguel Colina Castro, Elena Simone Benito, Raúl Torres-Ruiz, Sandra Rodriguez-Perales, Jonas Dehairs, Johannes V. Swinnen, Juan Carlos Garcia-Cañaveras, Agustín Lahoz, Sandra Montalvo Quirós, Carlos Pozo-Rojas, Clara Luque Rioja, Francisco Monroy, Diego Herráez-Aguilar, Marina Alonso Riaño, José Luis Rodríguez Peralto and Víctor Javier Sánchez-Arévalo Lobo ()
Additional contact information
Ana García García: Pozuelo de Alarcón
María Ferrer Aporta: Pozuelo de Alarcón
Germán Vallejo Palma: Avenida de Cordoba s/n
Antonio Giráldez Trujillo: Avenida de Cordoba s/n
Raquel Castillo-González: Avenida de Cordoba s/n
David Calzón Lozano: Pozuelo de Alarcón
Alberto Mora Perdiguero: Pozuelo de Alarcón
Raúl Muñoz Velasco: Pozuelo de Alarcón
Miguel Colina Castro: Pozuelo de Alarcón
Elena Simone Benito: Pozuelo de Alarcón
Raúl Torres-Ruiz: Centro Nacional de Investigaciones Oncológicas (CNIO)
Sandra Rodriguez-Perales: Centro Nacional de Investigaciones Oncológicas (CNIO)
Jonas Dehairs: KU Leuven
Johannes V. Swinnen: KU Leuven
Juan Carlos Garcia-Cañaveras: 106
Agustín Lahoz: 106
Sandra Montalvo Quirós: Pozuelo de Alarcón
Carlos Pozo-Rojas: Pozuelo de Alarcón
Clara Luque Rioja: Complutense University of Madrid
Francisco Monroy: Complutense University of Madrid
Diego Herráez-Aguilar: Pozuelo de Alarcón
Marina Alonso Riaño: Avenida de Cordoba s/n
José Luis Rodríguez Peralto: Avenida de Cordoba s/n
Víctor Javier Sánchez-Arévalo Lobo: Pozuelo de Alarcón

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: Abstract 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56894-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56894-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56894-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().