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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/124024
Ver los metadatos del registro completo
id |
SEDICI_4f2e2f8dd0945b50ed876d02064a284f |
---|---|
oai_identifier_str |
oai:sedici.unlp.edu.ar:10915/124024 |
network_acronym_str |
SEDICI |
repository_id_str |
1329 |
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 |
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 |
_version_ |
1844616173398786048 |
score |
13.070432 |