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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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
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spelling Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivityGarcía García, AnaFerrer Aporta, MaríaVallejo Palma, GermánGiráldez Trujillo, AntonioCastillo-González, RaquelCalzón Lozano, DavidMora Perdiguero, AlbertoMuñoz Velasco, RaúlColina Castro, Miguelde Simone Benito, ElenaTorres-Ruiz, RaúlRodriguez-Perales, SandraDehairs, JonasSwinnen, Johannes V.Garcia-Cañaveras, Juan CarlosLahoz, AgustínMontalvo Quirós, Sandradel Pozo-Rojas, CarlosLuque Rioja, ClaraMonroy, FranciscoHerráez-Aguilar, DiegoAlonso Riaño, MarinaRodríguez Peralto, José LuisSánchez-Arévalo Lobo, Víctor JavierGeneral ChemistryGeneral Biochemistry, Genetics and Molecular BiologyGeneral Physics and AstronomySDG 3 - Good Health and Well-beingYesyesPancreatic 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.Facultad de Ciencias ExperimentalesOncología Molecular20252025-12-0120252025-12-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/7147reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/71472026-06-11T12:44:57Z
dc.title.none.fl_str_mv Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
title Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
spellingShingle Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
García García, Ana
General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
SDG 3 - Good Health and Well-being
Yes
yes
title_short Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
title_full Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
title_fullStr Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
title_full_unstemmed Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
title_sort Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity
dc.creator.none.fl_str_mv 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
author García García, Ana
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias Experimentales
Oncología Molecular
dc.subject.none.fl_str_mv General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
SDG 3 - Good Health and Well-being
Yes
yes
topic General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
SDG 3 - Good Health and Well-being
Yes
yes
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-12-01
2025
2025-12-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/7147
url https://hdl.handle.net/10641/7147
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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