Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/169077
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Regulation of the prometastatic neuregulin–MMP13 axis by SRC family kinases: therapeutic implications |
Autor: | Orive-Ramos, Ana CSIC; Seoane, Samuel CSIC ORCID; Ocaña, Alberto; Pandiella, Atanasio CSIC ORCID CVN ; Montero, Juan Carlos CSIC ORCID | Palabras clave: | Breast cancer dissemination SRC Dasatinib MMP13 Neuregulin |
Fecha de publicación: | 2017 | Editor: | John Wiley & Sons Federation of European Biochemical Societies |
Citación: | Molecular Oncology 11(12): 1788-1805 (2017) | Resumen: | Metastatic dissemination of tumor cells is responsible for the fatal outcome of breast cancer. Therefore, understanding the mechanisms involved in dissemination is essential for the development of new therapeutic strategies to prevent metastasis. One mechanism involved in metastatic dissemination of breast cancer cells is dependent on control of the production of matrix metalloproteinases by the neuregulins (NRGs). The NRGs are polypeptide factors that act by binding to the ErbB/HER subfamily of receptor tyrosine kinases. NRG-mediated activation of HER receptors causes an increase in the production of metalloprotease 13 (MMP13, also termed collagenase-3), which facilitates metastatic dissemination of breast tumors. In this context, we aimed to explore whether the clinically approved tyrosine kinase inhibitor dasatinib was able to neutralize this mechanism of metastatic dissemination. Here, we show that dasatinib restricted NRG-induced MMP13 upregulation, both in vitro and in vivo, and in vivo metastatic dissemination of breast cancer cells. Chemical proteomics studies showed that the main cellular targets of dasatinib were SRC family kinases (SFKs). Moreover, genetic studies showed that knockdown of SRC or YES strongly inhibited NRG-induced MMP13 upregulation in vitro. Mechanistically, dasatinib treatment or knockdown of SRC also inhibited ERK1/2 kinases in vitro, which were required for NRG-induced MMP13 upregulation. These results open the possibility of clinically exploring the antitumoral action of dasatinib in those tumors in which the NRG–MMP13 signaling axis may play a relevant role in the control of tumor cell dissemination. | Versión del editor: | https://doi.org/10.1002/1878-0261.12145 | URI: | http://hdl.handle.net/10261/169077 | DOI: | 10.1002/1878-0261.12145 | Identificadores: | doi: 10.1002/1878-0261.12145 e-issn: 1878-0261 issn: 1574-7891 |
Aparece en las colecciones: | (IBMCC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
reguSRCimpli.pdf | 1,76 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
5
checked on 25-abr-2024
SCOPUSTM
Citations
6
checked on 23-abr-2024
WEB OF SCIENCETM
Citations
6
checked on 24-feb-2024
Page view(s)
286
checked on 03-may-2024
Download(s)
225
checked on 03-may-2024