Constitutive HER2 signaling promotes breast cancer metastasis through cellular senescence

Pier Davide Angelini, Mariano F. Zacarias Fluck, Kim Pedersen, Josep Lluiś Parra-Palau, Marc Guiu, Cristina Bernadó Morales, Rocio Vicario, Antonio Luque-Garciá, Nerea Peiró Navalpotro, Jordi Giralt, Francesc Canals, Roger R. Gomis, Josep Tabernero, José Baselga, Josep Villanueva, Joaquiń Arribas

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)

Abstract

Senescence, a terminal cell proliferation arrest, can be triggered by oncogenes. Oncogene-induced senescence is classically considered a tumor defense barrier. However, several findings show that, under certain circumstances, senescent cells may favor tumor progression because of their secretory phenotype. Here, we show that the expression in different breast epithelial cell lines of p95HER2, a constitutively active fragment of the tyrosine kinase receptor HER2, results in either increased proliferation or senescence. In senescent cells, p95HER2 elicits a secretome enriched in proteases, cytokines, and growth factors. This secretory phenotype is not a mere consequence of the senescence status and requires continuous HER2 signaling to be maintained. Underscoring the functional relevance of the p95HER2-induced senescence secretome, weshowthat p95HER2-induced senescent cells promote metastasis in vivo in a non-cell-autonomous manner. ©2012 AACR.
Original languageEnglish
Pages (from-to)450-458
JournalCancer Research
Volume73
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013

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