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
Ruoslahti, E., and Reed, J. C. (1994) Cell, 77, 477-478.
Frisch, S. M., Vuori, K., Ruoslahti, E., and Chan-Hui, P-Y. (1996) J. Cell Biol., 134, 793-799.
Khwaja, A., and Downward, J. (1997) J. Cell Biol., 139, 1017-1023.
Frisch, S. M., and Francis, H. (1994) J. Cell Biol., 124, 619-626.
Frisch, S. M., and Ruoslahti, E. (1997) Curr. Opin. Cell Biol., 9, 701-706.
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.
Berman, A. E., and Kozlova, N. I. (2000) Membr. Cell Biol., 13, 207-244.
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.
Eliceiri, B. P., and Cheresh, D. A. (1999) J. Clin. Invest., 103, 1227-1230.
Montgomery, A. M. P., Reisfeld, R. A., and Cheresh, D. (1994) Proc. Natl. Acad. Sci. USA, 91, 8856-8860.
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.
Stromblad, S., Becker, J. C., Yebra, M., Brooks, P. C., and Cheresh, D. A. (1996) J. Clin. Invest., 98, 426-433.
Brassard, D. L., Maxwell, E., Malkowski, M., Nagabhushan, T. L., Kumar, C. C., and Armstrong, L. (1999) Exp. Cell Res., 251, 33-45.
Berman, A., Morozevich, G., Karmansky, I., Gleiberman, T., and Bychkova, V. (1993) Biochem. Biophys. Res. Commun., 194, 351-357.
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.
Kozlova, N. I., Morozevich, G. E., Soloveyva, N. I., Vinokurova, S. V., and Berman, A. E. (1997) Biochem. Mol. Biol. Int., 43, 529-539.
Tang, D. G., Diglio, C. A., Bazaz, R., and Honn, K. V. (1995) J. Cell Sci., 108, 2629-2644.
Wyllie, A. (1980) Nature, 284, 555-556.
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.
Meredith, J. E., Fazeli, B., and Schwartz, M. A. (1993) Mol. Biol. Cell., 4, 953-961.
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.
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.
Zhang, Z., Vuori, K., Reed, J. C., and Ruoslahti, E. (1995) Proc. Natl. Acad. Sci. USA, 92, 6161-6165.
Vuori, K. (1998) J. Membr. Biol., 165, 191-199.
Howe, A., Aplin, A. E., Alahari, S. K., and Juliano, R. L. (1998) Curr. Opin. Cell Biol., 10, 220-231.
Eliceiri, B. P., Klemke, R., Stromblad, S., and Cheresh, D. A. (1998) J. Cell Biol., 140, 1255-1263.
Scatena, M., Almeida, M., Chaisson, M. L., Fausto, N., Nicosia, R. F., and Giachelli, C. M. (1998) J. Cell Biol., 141, 1083-1093.
Clarke, A., Lotz, M., Chao, C., and Mercurio, A. (1995) J. Biol. Chem., 270, 22673-22676.
Bachelder, R. E., Marchetti, A., Falcioni, R., Soddu, S., and Mercurio, A. M. (1999) J. Biol. Chem., 274, 20733-20737.
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.
Miao, J., Araki, S., Kaji, K., and Hayashi, H. (1997) Biochem. Biophys. Res. Commun., 233, 182-186.
Dowling, J., Yu, Q., and Fuchs, E. (1996) J. Cell Biol., 134, 559-572.
Stupack, D. G., Puente, X. S., Boutsaboualoy, S., Storgard, C. M., and Cheresh, D. A. (2001) J. Cell Biol., 155, 459-470.
Cheresh, D. A., and Stupack, D. G. (2002) Nature Med., 8, 193-194.
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.
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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