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ATM kinase sustains HER2 tumorigenicity in breast cancer

Author

Listed:
  • Venturina Stagni

    (Laboratory of Cell Signaling, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia
    University of Rome ‘Tor Vergata’)

  • Isabella Manni

    (Experimental Oncology, Regina Elena National Cancer Institute)

  • Veronica Oropallo

    (Laboratory of Cell Signaling, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia
    University of Rome ‘Tor Vergata’)

  • Marcella Mottolese

    (Regina Elena National Cancer Institute)

  • Anna Di Benedetto

    (Regina Elena National Cancer Institute)

  • Giulia Piaggio

    (Experimental Oncology, Regina Elena National Cancer Institute)

  • Rita Falcioni

    (Experimental Oncology, Regina Elena National Cancer Institute)

  • Danilo Giaccari

    (Laboratory of Cell Signaling, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia
    University of Rome ‘Tor Vergata’)

  • Selene Di Carlo

    (Experimental Oncology, Regina Elena National Cancer Institute
    Present address: Unité Microenvironnement et Immunité/Microenvironment and Immunity Unit, Pasteur Institut, 75724 Paris Cedex 15, France)

  • Francesca Sperati

    (Biostatistic Unit, Scientific Direction, Regina Elena National Cancer Institute)

  • Maria Teresa Cencioni

    (Laboratory of Neuroimmunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia)

  • Daniela Barilà

    (Laboratory of Cell Signaling, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia
    University of Rome ‘Tor Vergata’)

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 ATM’s tumorigenic potential revising the canonical role of ATM as a pure tumour suppressor.

Suggested Citation

  • Venturina Stagni & Isabella Manni & Veronica Oropallo & Marcella Mottolese & Anna Di Benedetto & Giulia Piaggio & Rita Falcioni & Danilo Giaccari & Selene Di Carlo & Francesca Sperati & Maria Teresa C, 2015. "ATM kinase sustains HER2 tumorigenicity in breast cancer," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7886
    DOI: 10.1038/ncomms7886
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