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, Gordon Mills, S. Dedhar, C. J. Marshall, W. J. Muller

Research output: Contribution to journalArticle

33 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Breast Neoplasms
Neoplasms
RNA Interference
Breast
Cell Death
Up-Regulation
Phosphorylation
integrin-linked kinase

Keywords

  • ErbB2
  • Integrin-linked kinase
  • Mammary tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Pontier, S. M., Huck, L., White, D. E., Rayment, J., Sanguin-Gendreau, V., Hennessy, B., ... 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

Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression : Implications for human breast cancer. / Pontier, S. M.; Huck, L.; White, D. E.; Rayment, J.; Sanguin-Gendreau, V.; Hennessy, B.; Zuo, D.; St-Arnaud, R.; Mills, Gordon; Dedhar, S.; Marshall, C. J.; Muller, W. J.

In: Oncogene, Vol. 29, No. 23, 10.06.2010, p. 3374-3385.

Research output: Contribution to journalArticle

Pontier, SM, Huck, L, White, DE, Rayment, J, Sanguin-Gendreau, V, Hennessy, B, Zuo, D, St-Arnaud, R, Mills, G, Dedhar, S, Marshall, CJ & Muller, WJ 2010, 'Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: Implications for human breast cancer', Oncogene, vol. 29, no. 23, pp. 3374-3385. https://doi.org/10.1038/onc.2010.86
Pontier SM, Huck L, White DE, Rayment J, Sanguin-Gendreau V, Hennessy B et al. Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: Implications for human breast cancer. Oncogene. 2010 Jun 10;29(23):3374-3385. https://doi.org/10.1038/onc.2010.86
Pontier, S. M. ; Huck, L. ; White, D. E. ; Rayment, J. ; Sanguin-Gendreau, V. ; Hennessy, B. ; Zuo, D. ; St-Arnaud, R. ; Mills, Gordon ; Dedhar, S. ; Marshall, C. J. ; Muller, W. J. / Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression : Implications for human breast cancer. In: Oncogene. 2010 ; Vol. 29, No. 23. pp. 3374-3385.
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