Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer

Overactivation of the human epidermal growth factor receptor 2 (HER2) is one of the main drivers of tamoxifen resistance in estrogen receptor (ER)-positive breast cancer patients. Combined targeting of HER2 and ER, however, has yielded disappointing results in the clinical setting. Therefore, other...

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Autores: Menendez, Javier A., Papadimitropoulou, Adriana, Steen, Travis Vander, Cuyàs, Elisabet, Oza Gajera, Bharvi P., Verdura, Sara, Espinoza, Ingrid, Vellón, Luciano, Mehmi, Inderjit, Lupu, Ruth
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/165308
Acceso en línea:http://hdl.handle.net/11336/165308
Access Level:acceso abierto
Palabra clave:ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
FATTY ACID SYNTHASE
HER2
TAMOXIFEN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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repository_id_str
spelling Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancerMenendez, Javier A.Papadimitropoulou, AdrianaSteen, Travis VanderCuyàs, ElisabetOza Gajera, Bharvi P.Verdura, SaraEspinoza, IngridVellón, LucianoMehmi, InderjitLupu, RuthENDOCRINE RESISTANCEESTROGEN RECEPTORFATTY ACID SYNTHASEHER2TAMOXIFENhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Overactivation of the human epidermal growth factor receptor 2 (HER2) is one of the main drivers of tamoxifen resistance in estrogen receptor (ER)-positive breast cancer patients. Combined targeting of HER2 and ER, however, has yielded disappointing results in the clinical setting. Therefore, other potential mechanisms for tamoxifen resistance would not be overcome by solely blocking the cross-talk between ER and HER2 at the receptor(s) level. Using cell lines, animal models, and clinical data, we provide evidence to support a critical role of fatty acid synthase (FASN)—the major site for endogenous fat synthesis—in HER2-driven tamoxifen resistance. Importantly, treatment with a FASN inhibitor impeded the estrogen-like tumor-promoting effects of tamoxifen and fully restored the anti-estrogenic activity of tamoxifen in ER+/HER2-overexpressing breast cancer xenografts. We postulate FASN as a biological determinant of HER2-driven tamoxifen resistance and FASN inhibition as a novel therapeutic approach to restore tamoxifen sensitivity in endocrine-resistant breast cancer.Fil: Menendez, Javier A.. Institut d'investigació Biomèdica de Girona Dr. Josep Trueta; España. Institut Català d'Oncologia; EspañaFil: Papadimitropoulou, Adriana. Academy of Athens; GreciaFil: Steen, Travis Vander. Mayo Clinic; Estados UnidosFil: Cuyàs, Elisabet. Institut d'investigació Biomèdica de Girona Dr. Josep Trueta; España. Institut Català d'Oncologia; EspañaFil: Oza Gajera, Bharvi P.. University of Cincinnati; Estados UnidosFil: Verdura, Sara. Institut d'investigació Biomèdica de Girona Dr. Josep Trueta; España. Institut Català d'Oncologia; EspañaFil: Espinoza, Ingrid. University of Mississippi; Estados UnidosFil: Vellón, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mehmi, Inderjit. The Angeles Clinic and Research Institute; Estados UnidosFil: Lupu, Ruth. Mayo Clinic; Estados UnidosMDPI AG2021-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/165308Menendez, Javier A.; Papadimitropoulou, Adriana; Steen, Travis Vander; Cuyàs, Elisabet; Oza Gajera, Bharvi P.; et al.; Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer; MDPI AG; Cancers; 13; 5; 3-2021; 1-192072-6694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/13/5/1132info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13051132info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:17:39Zoai:ri.conicet.gov.ar:11336/165308instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:17:39.4CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
title Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
spellingShingle Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
Menendez, Javier A.
ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
FATTY ACID SYNTHASE
HER2
TAMOXIFEN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
title_full Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
title_fullStr Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
title_full_unstemmed Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
title_sort Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer
dc.creator.none.fl_str_mv Menendez, Javier A.
Papadimitropoulou, Adriana
Steen, Travis Vander
Cuyàs, Elisabet
Oza Gajera, Bharvi P.
Verdura, Sara
Espinoza, Ingrid
Vellón, Luciano
Mehmi, Inderjit
Lupu, Ruth
author Menendez, Javier A.
author_facet Menendez, Javier A.
Papadimitropoulou, Adriana
Steen, Travis Vander
Cuyàs, Elisabet
Oza Gajera, Bharvi P.
Verdura, Sara
Espinoza, Ingrid
Vellón, Luciano
Mehmi, Inderjit
Lupu, Ruth
author_role author
author2 Papadimitropoulou, Adriana
Steen, Travis Vander
Cuyàs, Elisabet
Oza Gajera, Bharvi P.
Verdura, Sara
Espinoza, Ingrid
Vellón, Luciano
Mehmi, Inderjit
Lupu, Ruth
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
FATTY ACID SYNTHASE
HER2
TAMOXIFEN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic ENDOCRINE RESISTANCE
ESTROGEN RECEPTOR
FATTY ACID SYNTHASE
HER2
TAMOXIFEN
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Overactivation of the human epidermal growth factor receptor 2 (HER2) is one of the main drivers of tamoxifen resistance in estrogen receptor (ER)-positive breast cancer patients. Combined targeting of HER2 and ER, however, has yielded disappointing results in the clinical setting. Therefore, other potential mechanisms for tamoxifen resistance would not be overcome by solely blocking the cross-talk between ER and HER2 at the receptor(s) level. Using cell lines, animal models, and clinical data, we provide evidence to support a critical role of fatty acid synthase (FASN)—the major site for endogenous fat synthesis—in HER2-driven tamoxifen resistance. Importantly, treatment with a FASN inhibitor impeded the estrogen-like tumor-promoting effects of tamoxifen and fully restored the anti-estrogenic activity of tamoxifen in ER+/HER2-overexpressing breast cancer xenografts. We postulate FASN as a biological determinant of HER2-driven tamoxifen resistance and FASN inhibition as a novel therapeutic approach to restore tamoxifen sensitivity in endocrine-resistant breast cancer.
publishDate 2021
dc.date.none.fl_str_mv 2021-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/165308
Menendez, Javier A.; Papadimitropoulou, Adriana; Steen, Travis Vander; Cuyàs, Elisabet; Oza Gajera, Bharvi P.; et al.; Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer; MDPI AG; Cancers; 13; 5; 3-2021; 1-19
2072-6694
CONICET Digital
CONICET
url http://hdl.handle.net/11336/165308
identifier_str_mv Menendez, Javier A.; Papadimitropoulou, Adriana; Steen, Travis Vander; Cuyàs, Elisabet; Oza Gajera, Bharvi P.; et al.; Fatty acid synthase confers tamoxifen resistance to ER+/HER2+ breast cancer; MDPI AG; Cancers; 13; 5; 3-2021; 1-19
2072-6694
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/13/5/1132
info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13051132
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 15,811543

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