AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins

Autores
Riggio, Marina; Perrone, María C.; Polo, María L.; Rodríguez, María J.; May, María; Abba, Martín Carlos; Lanari, Claudia; Novaro, Virginia
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction. Thus, while overexpression of AKT1 promoted local tumor growth, downregulation of AKT1 or overexpression of AKT2 promoted peritumoral invasion and lung metastasis. Furthermore, we evaluated The Cancer Genome Atlas (TCGA) dataset for invasive breast carcinomas and found that increased AKT2 but not AKT1 mRNA levels correlated with a worse clinical outcome. We conclude that AKT isoforms play specific roles in different steps of breast cancer progression, with AKT1 involved in the local tumor growth and AKT2 involved in the distant tumor dissemination, having AKT2 a poorer prognostic value and consequently being a worthwhile target for therapy.
Facultad de Ciencias Naturales y Museo
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Materia
Ciencias Médicas
AKT1
AKT2
breast cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/87340
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/87340
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteinsRiggio, MarinaPerrone, María C.Polo, María L.Rodríguez, María J.May, MaríaAbba, Martín CarlosLanari, ClaudiaNovaro, VirginiaCiencias MédicasAKT1AKT2breast cancerThe purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction. Thus, while overexpression of AKT1 promoted local tumor growth, downregulation of AKT1 or overexpression of AKT2 promoted peritumoral invasion and lung metastasis. Furthermore, we evaluated The Cancer Genome Atlas (TCGA) dataset for invasive breast carcinomas and found that increased AKT2 but not AKT1 mRNA levels correlated with a worse clinical outcome. We conclude that AKT isoforms play specific roles in different steps of breast cancer progression, with AKT1 involved in the local tumor growth and AKT2 involved in the distant tumor dissemination, having AKT2 a poorer prognostic value and consequently being a worthwhile target for therapy.Facultad de Ciencias Naturales y MuseoCentro de Investigaciones Inmunológicas Básicas y Aplicadas2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/87340enginfo:eu-repo/semantics/altIdentifier/issn/2045-2322info:eu-repo/semantics/altIdentifier/doi/10.1038/srep44244info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:49:31Zoai:sedici.unlp.edu.ar:10915/87340Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:49:32.127SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
spellingShingle AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
Riggio, Marina
Ciencias Médicas
AKT1
AKT2
breast cancer
title_short AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_full AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_fullStr AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_full_unstemmed AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_sort AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
dc.creator.none.fl_str_mv Riggio, Marina
Perrone, María C.
Polo, María L.
Rodríguez, María J.
May, María
Abba, Martín Carlos
Lanari, Claudia
Novaro, Virginia
author Riggio, Marina
author_facet Riggio, Marina
Perrone, María C.
Polo, María L.
Rodríguez, María J.
May, María
Abba, Martín Carlos
Lanari, Claudia
Novaro, Virginia
author_role author
author2 Perrone, María C.
Polo, María L.
Rodríguez, María J.
May, María
Abba, Martín Carlos
Lanari, Claudia
Novaro, Virginia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
AKT1
AKT2
breast cancer
topic Ciencias Médicas
AKT1
AKT2
breast cancer
dc.description.none.fl_txt_mv The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction. Thus, while overexpression of AKT1 promoted local tumor growth, downregulation of AKT1 or overexpression of AKT2 promoted peritumoral invasion and lung metastasis. Furthermore, we evaluated The Cancer Genome Atlas (TCGA) dataset for invasive breast carcinomas and found that increased AKT2 but not AKT1 mRNA levels correlated with a worse clinical outcome. We conclude that AKT isoforms play specific roles in different steps of breast cancer progression, with AKT1 involved in the local tumor growth and AKT2 involved in the distant tumor dissemination, having AKT2 a poorer prognostic value and consequently being a worthwhile target for therapy.
Facultad de Ciencias Naturales y Museo
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
description The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction. Thus, while overexpression of AKT1 promoted local tumor growth, downregulation of AKT1 or overexpression of AKT2 promoted peritumoral invasion and lung metastasis. Furthermore, we evaluated The Cancer Genome Atlas (TCGA) dataset for invasive breast carcinomas and found that increased AKT2 but not AKT1 mRNA levels correlated with a worse clinical outcome. We conclude that AKT isoforms play specific roles in different steps of breast cancer progression, with AKT1 involved in the local tumor growth and AKT2 involved in the distant tumor dissemination, having AKT2 a poorer prognostic value and consequently being a worthwhile target for therapy.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/87340
url http://sedici.unlp.edu.ar/handle/10915/87340
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/2045-2322
info:eu-repo/semantics/altIdentifier/doi/10.1038/srep44244
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.13397

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