USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer

Autores
Rossi, Fabiana Alejandra; Enriqué Steinberg, Juliana Haydeé; Calvo Roitberg, Ezequiel Hernán; Joshi, Molishree; Pandey, Ahwan; Abba, Martín Carlos; Dufrusine, Beatrice; Buglioni, Simonetta; De Laurenzi, Vincenzo; Sala, Gianluca; Lattanzio, Rossano; Espinosa, Joaquín M.; Rossi, Mario
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigation in vivo and confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness both in vitro and in vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Materia
Medicina
Breast cancer
Functional genomics
Ubiquitylation
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:10915/124024

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network_name_str SEDICI (UNLP)
spelling USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancerRossi, Fabiana AlejandraEnriqué Steinberg, Juliana HaydeéCalvo Roitberg, Ezequiel HernánJoshi, MolishreePandey, AhwanAbba, Martín CarlosDufrusine, BeatriceBuglioni, SimonettaDe Laurenzi, VincenzoSala, GianlucaLattanzio, RossanoEspinosa, Joaquín M.Rossi, MarioMedicinaBreast cancerFunctional genomicsUbiquitylationTumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigation in vivo and confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness both in vitro and in vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicadas2021-03-13info: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/10915/124024enginfo:eu-repo/semantics/altIdentifier/issn/2157-9024info:eu-repo/semantics/altIdentifier/pmid/33714979info:eu-repo/semantics/altIdentifier/doi/10.1038/s41389-021-00318-xinfo: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:UNLP2025-09-29T11:29:28Zoai:sedici.unlp.edu.ar:10915/124024Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:29:28.71SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
title USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
spellingShingle USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
Rossi, Fabiana Alejandra
Medicina
Breast cancer
Functional genomics
Ubiquitylation
title_short USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
title_full USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
title_fullStr USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
title_full_unstemmed USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
title_sort USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
dc.creator.none.fl_str_mv Rossi, Fabiana Alejandra
Enriqué Steinberg, Juliana Haydeé
Calvo Roitberg, Ezequiel Hernán
Joshi, Molishree
Pandey, Ahwan
Abba, Martín Carlos
Dufrusine, Beatrice
Buglioni, Simonetta
De Laurenzi, Vincenzo
Sala, Gianluca
Lattanzio, Rossano
Espinosa, Joaquín M.
Rossi, Mario
author Rossi, Fabiana Alejandra
author_facet Rossi, Fabiana Alejandra
Enriqué Steinberg, Juliana Haydeé
Calvo Roitberg, Ezequiel Hernán
Joshi, Molishree
Pandey, Ahwan
Abba, Martín Carlos
Dufrusine, Beatrice
Buglioni, Simonetta
De Laurenzi, Vincenzo
Sala, Gianluca
Lattanzio, Rossano
Espinosa, Joaquín M.
Rossi, Mario
author_role author
author2 Enriqué Steinberg, Juliana Haydeé
Calvo Roitberg, Ezequiel Hernán
Joshi, Molishree
Pandey, Ahwan
Abba, Martín Carlos
Dufrusine, Beatrice
Buglioni, Simonetta
De Laurenzi, Vincenzo
Sala, Gianluca
Lattanzio, Rossano
Espinosa, Joaquín M.
Rossi, Mario
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Medicina
Breast cancer
Functional genomics
Ubiquitylation
topic Medicina
Breast cancer
Functional genomics
Ubiquitylation
dc.description.none.fl_txt_mv Tumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigation in vivo and confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness both in vitro and in vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
description Tumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigation in vivo and confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness both in vitro and in vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.
publishDate 2021
dc.date.none.fl_str_mv 2021-03-13
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/10915/124024
url http://sedici.unlp.edu.ar/handle/10915/124024
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/2157-9024
info:eu-repo/semantics/altIdentifier/pmid/33714979
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41389-021-00318-x
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
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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