The transmodulation of HER2 and EGFR by Substance P in breast cancer cells requires c-Src and metalloproteinase activation.

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RECERCAT Home > Universitat de Barcelona > IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer > Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) > View document

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dc.contributor.author	Garcia Recio, Susana
dc.contributor.author	Pastor Arroyo, Eva M.
dc.contributor.author	Marín Aguilera, Mercedes
dc.contributor.author	Almendro Navarro, Vanessa
dc.contributor.author	Gascón, Pere
dc.date	2018-02-27T18:22:16Z
dc.date	2018-02-27T18:22:16Z
dc.date	2015-06-26
dc.date	2018-02-27T18:22:16Z
dc.identifier	1932-6203
dc.identifier	677098
dc.identifier	26114632
dc.identifier.uri	http://hdl.handle.net/2445/120306
dc.description	BACKGROUND: Substance P (SP) is a pleiotropic cytokine/neuropeptide that enhances breast cancer (BC) aggressiveness by transactivating tyrosine kinase receptors like EGFR and HER2. We previously showed that SP and its cognate receptor NK-1 (SP/NK1-R) signaling modulates the basal phosphorylation of HER2 and EGFR in BC, increasing aggressiveness and drug resistance. In order to elucidate the mechanisms responsible for NK-1R-mediated HER2 and EGFR transactivation, we investigated the involvement of c-Src (a ligand-independent mediator) and of metalloproteinases (ligand-dependent mediators) in HER2/EGFR activation. RESULTS AND DISCUSSION: Overexpression of NK-1R in MDA-MB-231 and its chemical inhibition in SK-BR-3, BT-474 and MDA-MB-468 BC cells significantly modulated c-Src activation, suggesting that this protein is a mediator of NK-1R signaling. In addition, the c-Src inhibitor 4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2. On the other hand, SP-dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1-10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR. Moreover, the use of these inhibitors demonstrated that this Src and MMP-dependent signaling is important to the cell viability and migration capacity of HER2+ and EGFR+ cell lines. CONCLUSION: Our results indicate that the transactivation of HER2 and EGFR by the pro-inflammatory cytokine/neuropeptide SP in BC cells is a c-Src and MMP-dependent process.
dc.format	15 p.
dc.format	application/pdf
dc.language	eng
dc.publisher	Public Library of Science (PLoS)
dc.relation	Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0129661
dc.relation	PLoS One, 2015, vol. 10, num. 6, p. e0129661
dc.relation	https://doi.org/10.1371/journal.pone.0129661
dc.rights	cc-by (c) Garcia Recio, Susana et al., 2015
dc.rights	http://creativecommons.org/licenses/by/3.0/es
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Càncer de mama
dc.subject	Genètica molecular
dc.subject	Metal·loproteïnes
dc.subject	Breast cancer
dc.subject	Molecular genetics
dc.subject	Metalloproteins
dc.title	The transmodulation of HER2 and EGFR by Substance P in breast cancer cells requires c-Src and metalloproteinase activation.
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion

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