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

S. M. Pontier, L. Huck, D. E. White, J. Rayment, V. Sanguin-Gendreau, B. Hennessy, D. Zuo, R. St-Arnaud, G. B. Mills, S. Dedhar, C. J. Marshall, W. J. Muller

    Research output: Contribution to journalArticle

    34 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)3374-3385
    Number of pages12
    JournalOncogene
    Volume29
    Issue number23
    DOIs
    StatePublished - Jun 10 2010

    Keywords

    • ErbB2
    • Integrin-linked kinase
    • Mammary tumorigenesis

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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    Pontier, S. M., Huck, L., White, D. E., Rayment, J., Sanguin-Gendreau, V., Hennessy, B., Zuo, D., St-Arnaud, R., Mills, G. B., Dedhar, S., Marshall, C. J., & Muller, W. J. (2010). Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: Implications for human breast cancer. Oncogene, 29(23), 3374-3385. https://doi.org/10.1038/onc.2010.86