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Integrin αvβ3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells

Oncogene volume 20, pages 4710–4717 (2001)Cite this article

Abstract

A population of cells surviving during prolonged incubation in suspension (anoikis-negative cells) were selected from the original anoikis-positive human intestinal carcinoma cell line Caco-2. Anoikis-negative cells are characterized by a strong transcriptional downregulation of the αv-integrin chain as detected by FACS analysis, RT–PCR and Northern blotting. This finding suggested that αv-integrin generates a signal stimulating apoptosis of Caco-2 cells upon their detachment from the extracellular matrix. Two lines of evidence supporting this suggestion were provided. First, activation of the αvβ3 integrin on Caco-2 cells by their treatment with an αvβ3-specific monoclonal antibody resulted in marked stimulation of anoikis. Second, treatment of Caco-2 cells with αv-specific antisense oligonucleotide resulted in downregulation of the expression of αv chain and in elevated resistance of these cells to anoikis. Thus, for the first time, our data prove that αvβ3 integrin can be an active transducer of apoptosis-stimulating signals generated in response to disruption of the cell–matrix contacts.

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Acknowledgements

We wish to thank Alexander Tatosyan for discussion of experimental strategy and Irina Shirokova and Elena Musatkina for technical assistance. This work was supported by the Russian Foundation for Basic Research (grants 96-04-50543; 99-04-49344).

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  1. Institute of Biomedical Chemistry RAMS, Pogodinskaya Str. 10, Moscow, 119832, Russia

    Nadezda I Kozlova, Galina E Morozevich, Aleksandra N Chubukina & Albert E Berman

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  1. Nadezda I Kozlova
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  2. Galina E Morozevich
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  3. Aleksandra N Chubukina
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  4. Albert E Berman
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Correspondence to Albert E Berman.

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Kozlova, N., Morozevich, G., Chubukina, A. et al. Integrin αvβ3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells. Oncogene 20, 4710–4717 (2001). https://doi.org/10.1038/sj.onc.1204619

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