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αv integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells

Oncogene volume 22, pages 1688–1702 (2003)Cite this article

Abstract

Integrins regulate both adhesion and signaling processes involved in proliferation and survival. αvβ3 and αvβ5 integrins have been shown to mediate cell adhesion and migration. Here we used human ovarian cancer cell lines (IGROV1, SKOV-3) that express αvβ3 and αvβ5 to study their role in cell proliferation and the signaling pathways involved. We found that αv integrins regulate cell proliferation through activation of integrin-linked kinase (ILK). An anti-αv-blocking antibody specifically inhibits the growth of IGROV1 and SKOV-3. The inhibition of cell proliferation involves αvβ3 in IGROV1 cells, and both αvβ3 and αvβ5 in SKOV-3 cells. The reduced growth rate induced by αv integrin blockade is linked in both cell lines to G1/S cell cycle arrest. αv integrin blockade by neutralizing antibody as well as cyclic-RGD peptide caused an inhibition of ILK activity and phosphorylation of PKB/Akt on serine-473 but not on threonine-308, and was accompanied by an increase in p27Kip1 expression. Overexpression of wild-type ILK rescued the phosphorylation of PKB/Akt on serine-473 in cells treated with anti-αv antibody. Inhibition of ILK by a pharmacological inhibitor results in inhibition of cell proliferation, PKB/Akt phosphorylation and increase of p27Kip1. These results demonstrate that αv integrins regulate ovarian cancer cell proliferation through ILK.

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Acknowledgements

This work was supported by grants from the National Institute of Canada (NCIC) to S Dedhar, by the ‘Ligue Nationale contre le Cancer’ (Comité du Calvados, France) and ‘ Institut National de la Santé et de la Recherche Médicale’ (INSERM, France) to P Gauduchon and C Staedel. S Cruet-Hennequart is a recipient of a fellowship from the ‘Fondation pour la Recherche Médicale’ (FRM, France) and S Maubant from the ‘Ligue Nationale contre le Cancer’ (Comité du Calvados, France).

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Authors and Affiliations

  1. British Columbia Cancer Agency, Jack Bell Research Centre, 2660 Oak Street, Vancouver, V6 H 3Z6, British Columbia, Canada

    Séverine Cruet-Hennequart & Shoukat Dedhar

  2. Vancouver Hospital Health Science Center, Jack Bell Research Centre, 2660 Oak Street, Vancouver, V6, H 3Z6, Q1, British Columbia, Canada

    Séverine Cruet-Hennequart & Shoukat Dedhar

  3. Department of Biochemistry and Molecular Biology, University of British Columbia, British Columbia, Canada

    Séverine Cruet-Hennequart & Shoukat Dedhar

  4. Groupe Régional d'Etudes sur le Cancer (UPRES-EA 1772), Centre François Baclesse, route de Lion-sur-mer, Caen, Cedex 05, 14076, France

    Sylvie Maubant & Pascal Gauduchon

  5. UMR CNRS 6032, Laboratoire de Biochimie et Biologie Cellulaire, Faculté de Pharmacie, Boulevard Jean Moulin, Marseille Cedex, 13085, France

    José Luis

  6. INSERM U386, Université Bordeaux II, Bat.3A, 146, rue Léo Saignat, Bordeaux Cedex, 33076, France

    Cathy Staedel

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  1. Séverine Cruet-Hennequart
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Correspondence to Shoukat Dedhar.

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Cruet-Hennequart, S., Maubant, S., Luis, J. et al. αv integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells. Oncogene 22, 1688–1702 (2003). https://doi.org/10.1038/sj.onc.1206347

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