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

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...

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Autores principales: 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
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
Materias:
Medicina
Breast cancer
Functional genomics
Ubiquitylation
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/124024
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-124024
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Breast cancer
Functional genomics
Ubiquitylation
spellingShingle Medicina
Breast cancer
Functional genomics
Ubiquitylation
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
USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
topic_facet Medicina
Breast cancer
Functional genomics
Ubiquitylation
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.
format Articulo
Articulo
author 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_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_sort Rossi, Fabiana Alejandra
title USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
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
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/124024
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