Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

The integrin-linked kinase (ILK) suppresses anoikis

Oncogene volume 19, pages 3811–3815 (2000)Cite this article

Abstract

Disruption of integrin-extracellular matrix interactions in normal epithelial cells induces apoptosis, a process termed anoikis. Reduced sensitivity to anoikis appears to be an important hallmark of oncogenic transformation, particularly in the process of metastasis. Several pathways have been implicated in the suppression of anoikis, however, the events which take place proximal to the integrin receptors remain unclear. Integrin-linked kinase (ILK) is an integrin-interacting protein kinase which has been identified as a potential PDK-2, as it is capable of phosphorylating PKB/Akt on Ser-473, and stimulating its activity. Here, we show that ILK activity is stimulated upon adhesion of SCP2 mouse mammary epithelial cells to fibronectin, and inhibited in suspended cells. Overexpression of ILK in the anoikis-sensitive SCP2 cells results in a profound inhibition of anoikis, as determined by annexin V binding and activation of caspases 8 and 3. This effect is reversible by the transfection and expression of a dominant-negative, kinase deficient ILK (ILK KD), as well as by a dominant negative PKB/Akt (PKB AAA). On the other hand, transfection of a dominant negative form of FAK (FRNK) failed to reverse the suppression of anoikis by ILK. Furthermore, inhibition of ILK activity induced anoikis in two anoikis-resistant human breast cancer cell lines. These findings suggest that ILK plays a major role in the suppression of anoikis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Balendran A, Casamayor A, Deak M, Paterson A, Gaffney P, Currie R, Downes CP and Alessi DR. . 1999 Curr. Biol. 9: 393–404.

  • Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME. . 1999 Cell 96: 857–868.

  • Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME. . 1997 Cell 91: 231–241.

  • Delcommenne M, Tan C, Gray V, Ruel L, Woodgett J and Dedhar S. . 1998 Proc. Natl. Acad. Sci. USA 95: 11211–11216.

  • Downward J. . 1998 Curr. Biol. 10: 262–267.

  • Dragovich T, Rudin CM and Thompson CB. . 1998 Oncogene 17: 3207–3213.

  • Frisch SM. . 1999 Curr. Biol. 9: 1047–1049.

  • Frisch SM and Francis H. . 1994 J. Cell Biol. 124: 619–626.

  • Frisch SM and Ruoslahti E. . 1997 Curr. Biol. 9: 701–706.

  • Frisch S, Vuori K, Kelaita D and Sicks S. . 1996a J. Cell Biol. 135: 1377–1382.

  • Frisch S, Vuori K, Ruoslahti E and Chan-Hui PY. . 1996b J. Cell Biol. 134: 793–799.

  • Hannigan GE, Leung-Hagesteijn C, Fitzgibbon L, Coppolino M, Radeva G, Filmus J, Bell JC and Dedhar S. . 1996 Nature 379: 91–96.

  • Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH and Downward J. . 1997 EMBO J. 16: 2783–2793.

  • Kops GJ, de Ruiter ND, DeVries-Smits AM, Powell DR, Boss JL and Burgering BM. . 1999 Nature 398: 630–634.

  • Kumar C. . 1998 Oncogene 17: 1365–1373.

  • Lu Y, Lin YZ, LaPushin R, Cuevas B, Fang X, Yu SX, Davies MA, Khan H, Furui T, Mao M, Zinner R, Hung MC, Steck P, Siminovitch K and Mills GB. . 1999 Oncogene 18: 7034–7045.

  • Lynch DK, Ellis CA, Edwards PA and Hiles ID. . 1999 Oncogene 18: 8024–8032.

  • Morimoto AM, Tomlinson MG, Nakatini K, Bolen JB, Roth RA and Herbst R. . 2000 Oncogene 19: 200–209.

  • Novak A, Hsu SC, Leung-Hagesteijn C, Radeva G, Papkoff J, Montesano R, Roskelley C, Grosschedl R and Dedhar S. . 1998 Proc. Natl. Acad. Sci. USA 95: 4374–4379.

  • Persad S, Attwell S, Gray V, Delcommenne M, Troussard A, Sanghera J and Dedhar S. . 2000 Proc. Natl. Acad. Sci. USA 97: 3207–3212.

  • Radeva G, Petrocelli T, Behrend E, Leung-Hagesteijn C, Filmus J, Slingerland J and Dedhar S. . 1997 J. Biol. Chem. 272: 13937–13944.

  • Romashkova JA and Makarov SS. . 1999 Nature 401: 86–90.

  • Ruoslahti E and Reed J. . 1994 Cell 74: 477–478.

  • Rytomaa M, Martins ML and Downward J. . 1999 Curr. Biol. 9: 1043–1046.

  • Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski P and Mak TW. . 1998 Cell 95: 29–39.

  • Troussard A, Tan C, Yoganathan N and Dedhar S. . 1999 Mol. Cell. Biol. 19: 7420–7427.

  • Williams MR, C Arthur JS, Balendran A, van der Kaay J, Poli V, Cohen P and Alessi DR. . 2000 Curr. Biol. 10: 439–448.

  • Zhao JH, Reiske H and Guan JL. . 1998 J. Cell Biol. 143: 1997–2008.

Download references

Acknowledgements

We thank Kristina Vouri for the FRNK expression plasmid, and Kinetek Pharmaceuticals (Vancouver, Canada) for providing the ILK inhibitor, KP-SD1. This work was supported by grants to S Dedhar from the National Cancer Institute of Canada (NCIC). S Attwell is a recipient of a University Graduate Fellowship (UGF) from the University of British Columbia.

Author information

Authors and Affiliations

  1. British Columbia Cancer Agency and Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada

    Sarah Attwell & Shoukat Dedhar

  2. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6P 6P2, Canada

    Sarah Attwell & Shoukat Dedhar

  3. Department of Anatomy, University of British Columbia, Vancouver, BC V6T 1Z3, Canada

    Calvin Roskelley

Authors
  1. Sarah Attwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Calvin Roskelley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shoukat Dedhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Attwell, S., Roskelley, C. & Dedhar, S. The integrin-linked kinase (ILK) suppresses anoikis. Oncogene 19, 3811–3815 (2000). https://doi.org/10.1038/sj.onc.1203711

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203711

Keywords

This article is cited by

Search

Advanced search

Quick links