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Direct integrin αvβ6-ERK binding: implications for tumour growth

Oncogene volume 21, pages 1370–1380 (2002)Cite this article

Abstract

Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin αvβ6, in colon cancer cells. Down-regulation of β6 integrin subunit expression inhibits tumour growth in vivo and MAP kinase activity in response to serum stimulation. In αvβ6-expressing cells ERK2 is bound only to the β6 subunit. The increase in cytosolic MAP kinase activity upon epidermal growth factor stimulation is all accounted for by β6-bound ERK. Deletion of the ERK2 binding site on the β6 cytoplasmic domain inhibits tumour growth and leads to an association between ERK and the β5 subunit. The physical interaction between integrin αvβ6 and ERK2 defines a novel paradigm of integrin-mediated signalling and provides a therapeutic target for cancer treatment.

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Acknowledgements

We thank J Turton for assistance with preparation of the antisense β6. This work was supported jointly by grants from the New South Wales State Cancer Council, the National Health and Medical Research Council of Australia, The University of Newcastle Research Associates (TUNRA) Ltd. and the New South Wales Department of Health. MV Agrez was supported by a John Mitchell Crouch Fellowship from the Royal Australasian College of Surgeons. DJ Dorahy is and N Ahmed was a Brawn Postdoctoral Fellow, The University of Newcastle, New South Wales.

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Author notes

  1. Nuzhat Ahmed, Jun Niu and Douglas J Dorahy: N Ahmed, J Niu and DJ Dorahy contributed equally to this manuscript

Authors and Affiliations

  1. Newcastle Bowel Cancer Research Collaborative, Hunter Medical Research Institute, John Hunter Hospital and The University of Newcastle, Newcastle, New South Wales, Australia

    Jun Niu, Douglas J Dorahy, Xinhua Gu, Sarah Andrews, Cliff J Meldrum, Rodney J Scott & Michael V Agrez

  2. Gynaecological Cancer Research Centre, The Royal Women's Hospital, Melbourne and University of Melbourne, Melbourne, Australia

    Nuzhat Ahmed & Mark S Baker

  3. CSIRO Health Sciences and Nutrition, Parkville, Victoria, Australia

    Ian G Macreadie

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  1. Nuzhat Ahmed
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Correspondence to Michael V Agrez.

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Ahmed, N., Niu, J., Dorahy, D. et al. Direct integrin αvβ6-ERK binding: implications for tumour growth. Oncogene 21, 1370–1380 (2002). https://doi.org/10.1038/sj.onc.1205286

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