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

Author

Listed:
  • 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
    Universidad Autónoma de Madrid (UAM))

  • 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)
    Medioambientales y Tecnológicas (CIEMAT)
    Instituto de Investigación Sanitaria Fundación Jiménez Díaz
    Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER))

  • 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
    Avenida de Cordoba s/n)

  • Francisco Monroy

    (Complutense University of Madrid
    Avenida de Cordoba s/n)

  • 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
    Avenida de Cordoba s/n)

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.

Suggested Citation

  • 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 Coli, 2025. "Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56894-8
    DOI: 10.1038/s41467-025-56894-8
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    References listed on IDEAS

    as
    1. Jacopo Frallicciardi & Josef Melcr & Pareskevi Siginou & Siewert J. Marrink & Bert Poolman, 2022. "Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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