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CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response
The CUL4A E3 ubiquitin ligase is involved in the regulation of many cellular processes and its amplification and/or overexpression has been observed in breast cancer. The 13q34 amplification, which is associated with the basal-like breast cancer subtype, has been proposed as one of the mechanism beh...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039166/ https://www.ncbi.nlm.nih.gov/pubmed/24870930 |
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author | Saucedo-Cuevas, Laura P. Ruppen, Isabel Ximénez-Embún, Pilar Domingo, Samuel Gayarre, Javier Muñoz, Javier Silva, Jose M. García, María J. Benítez, Javier |
author_facet | Saucedo-Cuevas, Laura P. Ruppen, Isabel Ximénez-Embún, Pilar Domingo, Samuel Gayarre, Javier Muñoz, Javier Silva, Jose M. García, María J. Benítez, Javier |
author_sort | Saucedo-Cuevas, Laura P. |
collection | PubMed |
description | The CUL4A E3 ubiquitin ligase is involved in the regulation of many cellular processes and its amplification and/or overexpression has been observed in breast cancer. The 13q34 amplification, which is associated with the basal-like breast cancer subtype, has been proposed as one of the mechanism behind CUL4A up-regulation. However, the specific contribution of CUL4A to the biology of basal-like breast tumors has not yet been elucidated. In this work, by using cellular models of basal phenotype, we show the inhibitory effect of CUL4A silencing in the proliferation and growth of breast cancer cells both, in vitro and in vivo. We also demonstrate the transforming capacity of CUL4A exogenous overexpression in the 184B5 human mammary epithelial cells in vitro. Our results suggest a synergistic effect between CUL4A high levels and the activation of the RAS pathway in the tumorigenesis of basal-like breast cancer tumors. In addition, by using a proteomics approach we have defined novel candidate proteins and pathways that might mediate the oncogenic effect of CUL4A. In particular, we report a putative role of CUL4A in bypassing the immune system in breast cancer through the down-regulation of several molecules involved in the immune surveillance. These findings provide insight into the oncogenic properties of CUL4A in basal-like breast cancer and highlight the therapeutic opportunities to target CUL4A. |
format | Online Article Text |
id | pubmed-4039166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-40391662014-06-10 CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response Saucedo-Cuevas, Laura P. Ruppen, Isabel Ximénez-Embún, Pilar Domingo, Samuel Gayarre, Javier Muñoz, Javier Silva, Jose M. García, María J. Benítez, Javier Oncotarget Research Paper The CUL4A E3 ubiquitin ligase is involved in the regulation of many cellular processes and its amplification and/or overexpression has been observed in breast cancer. The 13q34 amplification, which is associated with the basal-like breast cancer subtype, has been proposed as one of the mechanism behind CUL4A up-regulation. However, the specific contribution of CUL4A to the biology of basal-like breast tumors has not yet been elucidated. In this work, by using cellular models of basal phenotype, we show the inhibitory effect of CUL4A silencing in the proliferation and growth of breast cancer cells both, in vitro and in vivo. We also demonstrate the transforming capacity of CUL4A exogenous overexpression in the 184B5 human mammary epithelial cells in vitro. Our results suggest a synergistic effect between CUL4A high levels and the activation of the RAS pathway in the tumorigenesis of basal-like breast cancer tumors. In addition, by using a proteomics approach we have defined novel candidate proteins and pathways that might mediate the oncogenic effect of CUL4A. In particular, we report a putative role of CUL4A in bypassing the immune system in breast cancer through the down-regulation of several molecules involved in the immune surveillance. These findings provide insight into the oncogenic properties of CUL4A in basal-like breast cancer and highlight the therapeutic opportunities to target CUL4A. Impact Journals LLC 2014-04-18 /pmc/articles/PMC4039166/ /pubmed/24870930 Text en Copyright: © 2014 Saucedo-Cuevas et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Saucedo-Cuevas, Laura P. Ruppen, Isabel Ximénez-Embún, Pilar Domingo, Samuel Gayarre, Javier Muñoz, Javier Silva, Jose M. García, María J. Benítez, Javier CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
title | CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
title_full | CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
title_fullStr | CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
title_full_unstemmed | CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
title_short | CUL4A contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
title_sort | cul4a contributes to the biology of basal-like breast tumors through modulation of cell growth and antitumor immune response |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039166/ https://www.ncbi.nlm.nih.gov/pubmed/24870930 |
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