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Role of Integrin αvβ3 in Substrate-Dependent Apoptosis of Human Intestinal Carcinoma Cells

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Abstract

Incubation of human intestinal carcinoma Caco-2 cells in suspension (i.e., in the absence of substrate contacts) leads to massive cell death by apoptosis. Since this type of apoptosis has been referred to as anoikis, we designated these cells as anoikis-positive. However, a minor proportion of Caco-2 cells, designated as anoikis-negative, survived in suspension. Extended incubation of the cells in suspension resulted in the reduction of the number of viable cells. In comparison to the original Caco-2 cell population, the anoikis-negative cells demonstrated markedly decreased levels of expression of integrin αvβ3 on the cell surface and of transcription of the αv subunit gene. Activation of the signaling function of αvβ3 in the original Caco-2 cells led to substantial stimulation of anoikis, while the inhibition of expression of this receptor resulted in better resistance of the cells to anoikis. The data provide the first evidence that αvβ3 integrin can generate apoptosis-stimulating signals.

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REFERENCES

  1. Ruoslahti, E., and Reed, J. C. (1994) Cell, 77, 477-478.

    Google Scholar 

  2. Frisch, S. M., Vuori, K., Ruoslahti, E., and Chan-Hui, P-Y. (1996) J. Cell Biol., 134, 793-799.

    Google Scholar 

  3. Khwaja, A., and Downward, J. (1997) J. Cell Biol., 139, 1017-1023.

    Google Scholar 

  4. Frisch, S. M., and Francis, H. (1994) J. Cell Biol., 124, 619-626.

    Google Scholar 

  5. Frisch, S. M., and Ruoslahti, E. (1997) Curr. Opin. Cell Biol., 9, 701-706.

    Google Scholar 

  6. Eble, J. A. (1997) in Molecular Biology Intelligence Unit. Integrin-Ligand Interaction (Eble, J. A., and Kunn, K., eds.) Chapman and Hall, New York, pp. 1-40.

    Google Scholar 

  7. Berman, A. E., and Kozlova, N. I. (2000) Membr. Cell Biol., 13, 207-244.

    Google Scholar 

  8. Brooks, P. C., Stromblad, S., Sanders, L. C., Schalscha, T. L., Aimes, R. T., Stetler-Stevenson, W. G., Quigley, J. P., and Cheresh, D. A. (1996) Cell, 85, 683-693.

    Google Scholar 

  9. Eliceiri, B. P., and Cheresh, D. A. (1999) J. Clin. Invest., 103, 1227-1230.

    Google Scholar 

  10. Montgomery, A. M. P., Reisfeld, R. A., and Cheresh, D. (1994) Proc. Natl. Acad. Sci. USA, 91, 8856-8860.

    Google Scholar 

  11. Brooks, P. C., Montgomery, A. M. P., Rosenfeld, M., Reisfeld, R. A., Hu, T., Klier, G., and Cheresh, D. A. (1994) Cell, 79, 1157-1164.

    Google Scholar 

  12. Stromblad, S., Becker, J. C., Yebra, M., Brooks, P. C., and Cheresh, D. A. (1996) J. Clin. Invest., 98, 426-433.

    Google Scholar 

  13. Brassard, D. L., Maxwell, E., Malkowski, M., Nagabhushan, T. L., Kumar, C. C., and Armstrong, L. (1999) Exp. Cell Res., 251, 33-45.

    Google Scholar 

  14. Berman, A., Morozevich, G., Karmansky, I., Gleiberman, T., and Bychkova, V. (1993) Biochem. Biophys. Res. Commun., 194, 351-357.

    Google Scholar 

  15. McGahon, A. J., Martin, S. J., Bissonette, R. P., Mahboubi, A., Shi, Y., Mogil, R. J., Nishioka, W. K., and Green, D. R. (1995) Meth. Cell Biol., 46, 153-185.

    Google Scholar 

  16. Kozlova, N. I., Morozevich, G. E., Soloveyva, N. I., Vinokurova, S. V., and Berman, A. E. (1997) Biochem. Mol. Biol. Int., 43, 529-539.

    Google Scholar 

  17. Tang, D. G., Diglio, C. A., Bazaz, R., and Honn, K. V. (1995) J. Cell Sci., 108, 2629-2644.

    Google Scholar 

  18. Wyllie, A. (1980) Nature, 284, 555-556.

    Google Scholar 

  19. Seftor, R. E. B., Seftor, E. A., Gehlsen, K. R., Stetler-Stevenson, W. G., Brown, P. D., Ruoslahti, E., and Hendrix, M. J. C. (1992) Proc. Natl. Acad. Sci. USA, 89, 1557-1561.

    Google Scholar 

  20. Meredith, J. E., Fazeli, B., and Schwartz, M. A. (1993) Mol. Biol. Cell., 4, 953-961.

    Google Scholar 

  21. Kuzuya, M., Satake, S., Ramos, M. A., Kanda, S., Koike, T., Yoshino, K., Ikeda, S., and Iguchi, A. (1999) Exp. Cell Res., 248, 498-508.

    Google Scholar 

  22. Taga, T., Suzuki, A., Gonzalez-Gomez, I., Gilles, F. H., Stins, M., Shimada, H., Barsky, L., Weinberg, K. I., and Laug, W. E. (2002) Int. J. Cancer, 98, 690-697.

    Google Scholar 

  23. Zhang, Z., Vuori, K., Reed, J. C., and Ruoslahti, E. (1995) Proc. Natl. Acad. Sci. USA, 92, 6161-6165.

    Google Scholar 

  24. Vuori, K. (1998) J. Membr. Biol., 165, 191-199.

    Google Scholar 

  25. Howe, A., Aplin, A. E., Alahari, S. K., and Juliano, R. L. (1998) Curr. Opin. Cell Biol., 10, 220-231.

    Google Scholar 

  26. Eliceiri, B. P., Klemke, R., Stromblad, S., and Cheresh, D. A. (1998) J. Cell Biol., 140, 1255-1263.

    Google Scholar 

  27. Scatena, M., Almeida, M., Chaisson, M. L., Fausto, N., Nicosia, R. F., and Giachelli, C. M. (1998) J. Cell Biol., 141, 1083-1093.

    Google Scholar 

  28. Clarke, A., Lotz, M., Chao, C., and Mercurio, A. (1995) J. Biol. Chem., 270, 22673-22676.

    Google Scholar 

  29. Bachelder, R. E., Marchetti, A., Falcioni, R., Soddu, S., and Mercurio, A. M. (1999) J. Biol. Chem., 274, 20733-20737.

    Google Scholar 

  30. Bachelder, R. E., Ribick, M. J., Marchetti, A., Falcioni, R., Soddu, S., Davis, K. R., and Mercurio, A. M. (1999) J. Cell Biol., 147, 1063-1072.

    Google Scholar 

  31. Miao, J., Araki, S., Kaji, K., and Hayashi, H. (1997) Biochem. Biophys. Res. Commun., 233, 182-186.

    Google Scholar 

  32. Dowling, J., Yu, Q., and Fuchs, E. (1996) J. Cell Biol., 134, 559-572.

    Google Scholar 

  33. Stupack, D. G., Puente, X. S., Boutsaboualoy, S., Storgard, C. M., and Cheresh, D. A. (2001) J. Cell Biol., 155, 459-470.

    Google Scholar 

  34. Cheresh, D. A., and Stupack, D. G. (2002) Nature Med., 8, 193-194.

    Google Scholar 

  35. Plath, T., Detjen, K., Welzel, M., von Marschall, Z., Murphy, D., Schirner, M., Wiedenmann, B., and Rosewicz, S. (2000) J. Cell Biol., 150, 1467-1477.

    Google Scholar 

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Morozevich, G.E., Kozlova, N.I., Chubukina, A.N. et al. Role of Integrin αvβ3 in Substrate-Dependent Apoptosis of Human Intestinal Carcinoma Cells. Biochemistry (Moscow) 68, 416–423 (2003). https://doi.org/10.1023/A:1023699829927

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  • DOI: https://doi.org/10.1023/A:1023699829927

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