Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer

Autores
Corominas Faja, Bruna; Vellón, Luciano; Cuyás, Elisabet; Buxó, María; Martin Castillo, Begoña; Serra, Dolors; García, Jordi; Menendez, Javier A.; Lupu, Ruth
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors were scored as FASN overexpressors in a series of almost 200 patients with invasive breast carcinoma. Re-classification of HER2-positive breast tumors based on FASN gene expression predicted a significantly inferior relapse-free and distant metastasis-free survival in HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells engineered to overexpress HER2 upregulated FASN gene expression, and the FASN inhibitor C75 abolished HER2-induced anchorage-independent growth and survival. Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7 breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic concentrations significantly reduced the capacity of MCF-7/HER2 cells to form mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of breast cancer patients that might benefit from treatment with therapeutic regimens containing FASN inhibitors.
Fil: Corominas Faja, Bruna. Instituto Catalan de Oncología; España. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España
Fil: 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; Argentina
Fil: Cuyás, Elisabet. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España. Instituto Catalán de Oncología; España
Fil: Buxó, María. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España
Fil: Martin Castillo, Begoña. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España. Instituto Catalán de Oncología; España
Fil: Serra, Dolors. Universidad de Barcelona; España
Fil: García, Jordi. Universidad de Barcelona; España
Fil: Menendez, Javier A.. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; ; España. Instituto Catalán de Oncología; España
Fil: Lupu, Ruth. Mayo Medical School. Mayo Clinic; Estados Unidos
Materia
Fatty Acid Synthase
Her2
Breast Cancer
C75
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24575
Acceder
id CONICETDig_8e88299dc3e05f78b460ad1073155611
oai_identifier_str oai:ri.conicet.gov.ar:11336/24575
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancerCorominas Faja, BrunaVellón, LucianoCuyás, ElisabetBuxó, MaríaMartin Castillo, BegoñaSerra, DolorsGarcía, JordiMenendez, Javier A.Lupu, RuthFatty Acid SynthaseHer2Breast CancerC75https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors were scored as FASN overexpressors in a series of almost 200 patients with invasive breast carcinoma. Re-classification of HER2-positive breast tumors based on FASN gene expression predicted a significantly inferior relapse-free and distant metastasis-free survival in HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells engineered to overexpress HER2 upregulated FASN gene expression, and the FASN inhibitor C75 abolished HER2-induced anchorage-independent growth and survival. Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7 breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic concentrations significantly reduced the capacity of MCF-7/HER2 cells to form mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of breast cancer patients that might benefit from treatment with therapeutic regimens containing FASN inhibitors.Fil: Corominas Faja, Bruna. Instituto Catalan de Oncología; España. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; EspañaFil: 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: Cuyás, Elisabet. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España. Instituto Catalán de Oncología; EspañaFil: Buxó, María. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; EspañaFil: Martin Castillo, Begoña. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España. Instituto Catalán de Oncología; EspañaFil: Serra, Dolors. Universidad de Barcelona; EspañaFil: García, Jordi. Universidad de Barcelona; EspañaFil: Menendez, Javier A.. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; ; España. Instituto Catalán de Oncología; EspañaFil: Lupu, Ruth. Mayo Medical School. Mayo Clinic; Estados UnidosUniversidad de Murcia2017-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24575Corominas Faja, Bruna; Vellón, Luciano; Cuyás, Elisabet; Buxó, María; Martin Castillo, Begoña; et al.; Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer; Universidad de Murcia; Histology and Histopathology; 32; 7; 7-2017; 687-6980213-39111699-5848CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.hh.um.es/Abstracts/Vol_32/32_7/32_7_687.htminfo:eu-repo/semantics/altIdentifier/doi/10.14670/HH-11-830info:eu-repo/semantics/altIdentifier/pmid/27714708info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:46Zoai:ri.conicet.gov.ar:11336/24575instacron: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:34982025-09-29 10:06:46.758CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
title Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
spellingShingle Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
Corominas Faja, Bruna
Fatty Acid Synthase
Her2
Breast Cancer
C75
title_short Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
title_full Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
title_fullStr Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
title_full_unstemmed Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
title_sort Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer
dc.creator.none.fl_str_mv Corominas Faja, Bruna
Vellón, Luciano
Cuyás, Elisabet
Buxó, María
Martin Castillo, Begoña
Serra, Dolors
García, Jordi
Menendez, Javier A.
Lupu, Ruth
author Corominas Faja, Bruna
author_facet Corominas Faja, Bruna
Vellón, Luciano
Cuyás, Elisabet
Buxó, María
Martin Castillo, Begoña
Serra, Dolors
García, Jordi
Menendez, Javier A.
Lupu, Ruth
author_role author
author2 Vellón, Luciano
Cuyás, Elisabet
Buxó, María
Martin Castillo, Begoña
Serra, Dolors
García, Jordi
Menendez, Javier A.
Lupu, Ruth
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fatty Acid Synthase
Her2
Breast Cancer
C75
topic Fatty Acid Synthase
Her2
Breast Cancer
C75
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors were scored as FASN overexpressors in a series of almost 200 patients with invasive breast carcinoma. Re-classification of HER2-positive breast tumors based on FASN gene expression predicted a significantly inferior relapse-free and distant metastasis-free survival in HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells engineered to overexpress HER2 upregulated FASN gene expression, and the FASN inhibitor C75 abolished HER2-induced anchorage-independent growth and survival. Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7 breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic concentrations significantly reduced the capacity of MCF-7/HER2 cells to form mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of breast cancer patients that might benefit from treatment with therapeutic regimens containing FASN inhibitors.
Fil: Corominas Faja, Bruna. Instituto Catalan de Oncología; España. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España
Fil: 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; Argentina
Fil: Cuyás, Elisabet. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España. Instituto Catalán de Oncología; España
Fil: Buxó, María. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España
Fil: Martin Castillo, Begoña. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; España. Instituto Catalán de Oncología; España
Fil: Serra, Dolors. Universidad de Barcelona; España
Fil: García, Jordi. Universidad de Barcelona; España
Fil: Menendez, Javier A.. Instituto de Investigación Biomédica de Girona Dr. Josep Trueta IdIBGi; ; España. Instituto Catalán de Oncología; España
Fil: Lupu, Ruth. Mayo Medical School. Mayo Clinic; Estados Unidos
description Fatty acid synthase (FASN) is a key lipogenic enzyme for de novo fatty acid biosynthesis and a druggable metabolic oncoprotein that is activated in most human cancers. We evaluated whether the HER2-driven lipogenic phenotype might represent a biomarker for sensitivity to pharmacological FASN blockade. A majority of clinically HER2-positive tumors were scored as FASN overexpressors in a series of almost 200 patients with invasive breast carcinoma. Re-classification of HER2-positive breast tumors based on FASN gene expression predicted a significantly inferior relapse-free and distant metastasis-free survival in HER2+/FASN+ patients. Notably, non-tumorigenic MCF10A breast epithelial cells engineered to overexpress HER2 upregulated FASN gene expression, and the FASN inhibitor C75 abolished HER2-induced anchorage-independent growth and survival. Furthermore, in the presence of high concentrations of C75, HER2-negative MCF-7 breast cancer cells overexpressing HER2 (MCF-7/HER2) had significantly higher levels of apoptosis than HER2-negative cells. Finally, C75 at non-cytotoxic concentrations significantly reduced the capacity of MCF-7/HER2 cells to form mammospheres, an in vitro indicator of cancer stem-like cells. Collectively, our findings strongly suggest that the HER2-FASN lipogenic axis delineates a group of breast cancer patients that might benefit from treatment with therapeutic regimens containing FASN inhibitors.
publishDate 2017
dc.date.none.fl_str_mv 2017-07
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/11336/24575
Corominas Faja, Bruna; Vellón, Luciano; Cuyás, Elisabet; Buxó, María; Martin Castillo, Begoña; et al.; Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer; Universidad de Murcia; Histology and Histopathology; 32; 7; 7-2017; 687-698
0213-3911
1699-5848
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24575
identifier_str_mv Corominas Faja, Bruna; Vellón, Luciano; Cuyás, Elisabet; Buxó, María; Martin Castillo, Begoña; et al.; Clinical and therapeutic relevance of the metabolic oncogene fatty acid synthase in HER2+ breast cancer; Universidad de Murcia; Histology and Histopathology; 32; 7; 7-2017; 687-698
0213-3911
1699-5848
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.hh.um.es/Abstracts/Vol_32/32_7/32_7_687.htm
info:eu-repo/semantics/altIdentifier/doi/10.14670/HH-11-830
info:eu-repo/semantics/altIdentifier/pmid/27714708
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidad de Murcia
publisher.none.fl_str_mv Universidad de Murcia
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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 13.070432

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