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Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer

Oncogene volume 29, pages 3374–3385 (2010)Cite this article

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Abstract

Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction.

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Acknowledgements

We are grateful to Cynthia Lavoie, Vassilios Papavassiliou, Celine Champigny and Kay Savage for excellent technical help during the project. We also thank all members of the Muller laboratory for their critical commentaries as well as Richard Lamb and Maria Cerone for critical discussions and reading. SMP was funded by a fellowship of The Terry Fox Foundation through an award from the National Cancer Institute of Canada (NCIC). DW was funded by the US Department of Defense (BCRP/CDMRP Era of Hope Postdoctoral award) as well as JR. CJM is a Cancer Research UK Gibb Fellow. WJM was supported by CRC Chair in Molecular Oncology. This work was supported by grants from Cancer Research UK, the Canadian Institutes of Health Research (CIHR)/Canadian Breast Cancer Research Alliance (CBCRA) (#64280), the US Department of Defense and the National Institutes of Health 5PO1GA-099031-05.

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Author notes

  1. S M Pontier, L Huck and D E White: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada

    S M Pontier, L Huck, J Rayment, V Sanguin-Gendreau, D Zuo & W J Muller

  2. Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, London, UK

    D E White & C J Marshall

  3. Department of Systems Biology, The University of Texas MD Anderson Cancer Centre, Houston, TX, USA

    B Hennessy & G B Mills

  4. Genetics Unit, Shriners Hospital, Montreal, Quebec, Canada

    R St-Arnaud

  5. Department of Biochemistry, BC Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada

    S Dedhar

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  1. S M Pontier
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Correspondence to W J Muller.

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Pontier, S., Huck, L., White, D. et al. Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer. Oncogene 29, 3374–3385 (2010). https://doi.org/10.1038/onc.2010.86

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