ATM kinase sustains HER2 tumorigenicity in breast cancer

Venturina Stagni, Isabella Manni, Veronica Oropallo, Marcella Mottolese, Anna Di Benedetto, Giulia Piaggio, Rita Falcioni, Danilo Giaccari, Selene Di Carlo, Francesca Sperati, Maria Teresa Cencioni, Daniela Barilà

Research output: Contribution to journalArticle

Abstract

ATM kinase preserves genomic stability by acting as a tumour suppressor. However, its identification as a component of several signalling networks suggests a dualism for ATM in cancer. Here we report that ATM expression and activity promotes HER2-dependent tumorigenicity in vitro and in vivo. We reveal a correlation between ATM activation and the reduced time to recurrence in patients diagnosed with invasive HER2-positive breast cancer. Furthermore, we identify ATM as a novel modulator of HER2 protein stability that acts by promoting a complex of HER2 with the chaperone HSP90, therefore preventing HER2 ubiquitination and degradation. As a consequence, ATM sustains AKT activation downstream of HER2 and may modulate the response to therapeutic approaches, suggesting that the status of ATM activity may be informative for the treatment and prognosis of HER2-positive tumours. Our findings provide evidence for ATMâ €™ s tumorigenic potential revising the canonical role of ATM as a pure tumour suppressor

Original languageEnglish
Article number6886
JournalNature Communications
Volume6
DOIs
Publication statusPublished - Apr 16 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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