The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma

Autores
Melana Colavita, Juan Pablo; Mignolli, Francesco; Stoyanoff, Tania Romina; Aguirre, María Victoria; Balboa, María A.; Balsinde Rodríguez, Jesús; Rodríguez, Juan Pablo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.
Fil: Melana Colavita, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Mignolli, Francesco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina
Fil: Stoyanoff, Tania Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Aguirre, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Balboa, María A.. Consejo Superior de Investigaciones Científicas; España. Universidad de Valladolid; España
Fil: Balsinde Rodríguez, Jesús. Consejo Superior de Investigaciones Científicas; España. Universidad de Valladolid; España
Fil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Materia
HYPOXIA
KIDNEY
OLEIC ACID
SCD-1
TUMOR MICROENVIRONMENT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/170671
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinomaMelana Colavita, Juan PabloMignolli, FrancescoStoyanoff, Tania RominaAguirre, María VictoriaBalboa, María A.Balsinde Rodríguez, JesúsRodríguez, Juan PabloHYPOXIAKIDNEYOLEIC ACIDSCD-1TUMOR MICROENVIRONMENThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.Fil: Melana Colavita, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Mignolli, Francesco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Stoyanoff, Tania Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Aguirre, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Balboa, María A.. Consejo Superior de Investigaciones Científicas; España. Universidad de Valladolid; EspañaFil: Balsinde Rodríguez, Jesús. Consejo Superior de Investigaciones Científicas; España. Universidad de Valladolid; EspañaFil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaMDPI2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/170671Melana Colavita, Juan Pablo; Mignolli, Francesco; Stoyanoff, Tania Romina; Aguirre, María Victoria; Balboa, María A.; et al.; The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma; MDPI; Cancers; 13; 12; 6-2021; 1-152072-6694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/13/12/2962info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13122962info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:58:20Zoai:ri.conicet.gov.ar:11336/170671instacron: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:34982025-11-12 09:58:20.291CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
title The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
spellingShingle The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
Melana Colavita, Juan Pablo
HYPOXIA
KIDNEY
OLEIC ACID
SCD-1
TUMOR MICROENVIRONMENT
title_short The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
title_full The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
title_fullStr The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
title_full_unstemmed The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
title_sort The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma
dc.creator.none.fl_str_mv Melana Colavita, Juan Pablo
Mignolli, Francesco
Stoyanoff, Tania Romina
Aguirre, María Victoria
Balboa, María A.
Balsinde Rodríguez, Jesús
Rodríguez, Juan Pablo
author Melana Colavita, Juan Pablo
author_facet Melana Colavita, Juan Pablo
Mignolli, Francesco
Stoyanoff, Tania Romina
Aguirre, María Victoria
Balboa, María A.
Balsinde Rodríguez, Jesús
Rodríguez, Juan Pablo
author_role author
author2 Mignolli, Francesco
Stoyanoff, Tania Romina
Aguirre, María Victoria
Balboa, María A.
Balsinde Rodríguez, Jesús
Rodríguez, Juan Pablo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HYPOXIA
KIDNEY
OLEIC ACID
SCD-1
TUMOR MICROENVIRONMENT
topic HYPOXIA
KIDNEY
OLEIC ACID
SCD-1
TUMOR MICROENVIRONMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.
Fil: Melana Colavita, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Mignolli, Francesco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentina
Fil: Stoyanoff, Tania Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Aguirre, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Balboa, María A.. Consejo Superior de Investigaciones Científicas; España. Universidad de Valladolid; España
Fil: Balsinde Rodríguez, Jesús. Consejo Superior de Investigaciones Científicas; España. Universidad de Valladolid; España
Fil: Rodríguez, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
description Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma (RCC). It is characterized by a high cell proliferation and the ability to store lipids. Previous studies have demonstrated the overexpression of enzymes associated with lipid metabolism, including stearoyl-CoA desaturase-1 (SCD-1), which increases the concentration of unsaturated fatty acids in tumor cells. In this work, we studied the expression of SCD-1 in primary ccRCC tumors, as well as in cell lines, to determine its influence on the tumor lipid composition and its role in cell proliferation. The lipidomic analyses of patient tumors showed that oleic acid (18:1n-9) is one of the major fatty acids, and it is particularly abundant in the neutral lipid fraction of the tumor core. Using a ccRCC cell line model and in vitro-generated chemical hypoxia, we show that SCD-1 is highly upregulated (up to 200-fold), and this causes an increase in the cellular level of 18:1n-9, which, in turn, accumulates in the neutral lipid fraction. The pharmacological inhibition of SCD-1 blocks 18:1n-9 synthesis and compromises the proliferation. The addition of exogenous 18:1n-9 to the cells reverses the effects of SCD-1 inhibition on cell proliferation. These data reinforce the role of SCD-1 as a possible therapeutic target.
publishDate 2021
dc.date.none.fl_str_mv 2021-06
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/11336/170671
Melana Colavita, Juan Pablo; Mignolli, Francesco; Stoyanoff, Tania Romina; Aguirre, María Victoria; Balboa, María A.; et al.; The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma; MDPI; Cancers; 13; 12; 6-2021; 1-15
2072-6694
CONICET Digital
CONICET
url http://hdl.handle.net/11336/170671
identifier_str_mv Melana Colavita, Juan Pablo; Mignolli, Francesco; Stoyanoff, Tania Romina; Aguirre, María Victoria; Balboa, María A.; et al.; The hypoxic microenvironment induces stearoyl-coa desaturase-1 overexpression and lipidomic profile changes in clear cell renal cell carcinoma; MDPI; Cancers; 13; 12; 6-2021; 1-15
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/2072-6694/13/12/2962
info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers13122962
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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