Résumés
Résumé
Les mécanismes de la régulation de la survie cellulaire et de l’apoptose sont d’une nature très complexe, impliquant de nombreux intervenants et de nombreuses voies de signalisation aussi bien dans la prise de décision de survivre (ou de mourir) que dans l’exécution de l’apoptose proprement dite. Il en va de même pour l’anoïkose, une forme d’apoptose régulée principalement par les interactions cellule-matrice extracellulaire médiées par les intégrines. Or, la survie cellulaire, l’apoptose et l’anoïkose comportent des différences mécanistiques supplémentaires dépendant des tissus et des types cellulaires spécifiquement concernés. Incidemment, des études de la survie cellulaire effectuées dans un tissu particulier, l’épithélium intestinal humain, ont mis au jour un degré additionnel de complexité dans la régulation de ces processus : l’activation de mécanismes distincts selon l’état de différenciation cellulaire.
Summary
The regulatory mechanisms of cell survival and apoptosis are very complex in nature, implicating numerous players and signaling pathways not only in the decision-making process of surviving (or dying), but as well as in the execution of apoptosis itself. The same complex nature applies with regards to anoikis, a form of apoptosis that is largely regulated by integrin-mediated, cell-extracellular matrix interactions. However, cell survival, apoptosis and anoikis also happen to implicate further mechanistic distinctions according to the specific tissue and/or cell type concerned. Incidentally, recent studies in a particular tissue, the human intestinal epithelium, have unearthed yet another layer of complexity in the regulation of these three cellular processes, namely the implication of differentiation state-specific mechanisms. Although our understanding of the molecular underpinnings of this new concept of differentiation state-distinct regulation of cell survival, apoptosis and/or anoikis is in its infancy, there is already evidence that such principle applies as well to cell types other than intestinal epithelial cells. Further studies on the differentiation state-specific regulation of these three cellular processes, either under normal or physiopathological situations, should prove crucial in increasing our understanding of pathologies which implicate a dysregulation of apoptosis and/or anoikis – such as cancer.
Parties annexes
Références
- 1. Edinger AL, Thompson CB. Death by design : apoptosis, necrosis and autophagy. Curr Opin Cell Biol 2004 ; 16 : 663-9.
- 2. Cory S, Huang DCS, Adams JM. The Bcl-2 family : roles in cell survival and oncogenesis. Oncogene 2003 ; 22 : 8590-7.
- 3. Martin SS, Vuori K. Regulation of Bcl-2 proteins during anoikis and amorphosis. Biochim Biophys Acta 2004 ; 1692 : 145-7.
- 4. Fuentes-Prior P, Salvesen G. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J 2004, 384 : 201-22.
- 5. Beaulieu JF. Integrins and human intestinal cell functions. Front Biosci 1999 ; 4 : 310-21.
- 6. Boudreau NJ, Jones PL. Extracellular matrix and integrin signaling : the shape of things to come. Biochem J 1999 ; 339 : 481-8.
- 7. Giancotti FG, Ruoslahti E. Integrin signaling. Science 1999 ; 285 : 1028-32.
- 8. Giancotti FG. Complexity and specificity of integrin signaling. Nat Cell Biol 1999 ; 2 : E13-4.
- 9. Hynes RO. Integrins : bidirectional, allosteric signaling machines. Cell 2002, 110 : 673-87.
- 10. Frisch SM, Screaton RA. Anoikis mechanisms. Curr Opin Cell Biol 2001 ; 13 : 555-62.
- 11. Grossmann J. Molecular mechanisms of « detachment-induced apoptosis-anoikis ». Apoptosis 2002 ; 7 : 247-260.
- 12. Stupack DG, Cheresh DA. Get a ligand, get a life : integrins, signaling and cell survival. J Cell Sci 2002 ; 115 : 3729-38.
- 13. Ameisen JC. Anoïkis. Med Sci (Paris) 2005 ; 21 : 117.
- 14. Cornillion J, Campos L, Guyotat D. Focal adhesion kinase (FAK), une protéine aux fonctions multiples. Med Sci (Paris) 2003 ; 19 : 743-52.
- 15. Giancotti FG. Integrin signaling : specificity and control of cell survival and cell cycle progression. Curr Opin Cell Biol 1997 ; 9 : 691-700.
- 16. Kim D, Dan HC, Park S, et al. AKT/PKB signaling mechanisms in cancer and chemoresistance. Front Biosci 2005, 10 : 975-87.
- 17. Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 2005 ; 9 : 59-71.
- 18. Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001 ; 81 : 807-69.
- 19. Dufour G., Demers MJ, Gagné D, et al. Human intestinal epithelial cell survival and anoikis : differentiation state-distinct regulation and roles of protein kinase B/Akt isoforms. J Biol Chem 2004 ; 279 : 44113-22.
- 20. Gauthier R, Laprise P, Cardin É, et al. Differential sensitivity to apoptosis between the human small and large intestinal mucosae : linkage with segment-specific regulation of Bcl-2 homologs and involvement of signaling pathways. J Cell Biochem 2001 ; 82 : 339-55.
- 21. Gauthier R, Harnois C, Drolet JF, et al. Human intestinal epithelial cell survival : differentiation state-specific control mechanisms. Am J Physiol 2001 ; 280 : C1540-54.
- 22. Harnois C, Demers M-J, Bouchard V, et al. Human intestinal epithelial crypt cell survival and death : complex modulations of Bcl-2 homologs by Fak, PI3-K/Akt-1, MEK/Erk, and p38 signaling pathways. J Cell Physiol 2004 ; 198 : 209-22.
- 23. Laprise P, Vallée K, Demers MJ, et al. Merosin (laminin-2/4)-driven survival signaling : complex modulations of Bcl-2 homologs. J Cell Biochem 2003 ; 89 : 1115-25.
- 24. Laprise P, Poirier ÈM, Vézina A, et al. Merosin-integrin promotion of skeletal myofiber cell survival : differentiation state-distinct involvement of p60Fyn tyrosine kinase and p38α stress-activated MAP kinase. J Cell Physiol 2002 ; 191 : 69-81.
- 25. Vachon PH, Harnois C, Grenier A, et al. Differentiation state-selective roles of p38 isoforms in human intestinal epithelial cell anoikis. Gastroenterology 2002 ; 123 : 1980-91.
- 26. Shohat G, Shani G, Eisenstein M, Kimchi A. The DAP-kinase family of proteins : study of a novel group of calcium-regulated death-promoting kinases. Biochim Biophys Acta 2002 ; 1600 : 45-50.
- 27. Ménard D, Beaulieu JF, Boudreau F, Perreault N, Rivard N, Vachon PH. Gastrointestinal tract (GI tract). In : Unsicker K, Krieglstein K, eds. Cell signaling and growth factors in development. Verlag : Wiley-VCH, 2005 :755-90.
- 28. Vachon PH, Cardin É, Harnois C, et al. Early establishment of epithelial apoptosis in the developing human small intestine. Int J Dev Biol 2000 ; 44 : 891-8.
- 29. Vachon PH, Cardin E, Harnois C, et al. Early acquisition of bowel segment-specific Bcl-2 expression profiles during the development of the human ileum and colon. Histol Histopathol 2001 ; 16 : 497-510.
- 30. Vachon PH, Loechel F, Xu H, et al. Merosin and laminin in myogenesis : specific requirement for merosin in myotube stability and survival. J Cell Biol 1996 ; 134 : 1483-97.
- 31. Vachon PH, Xu H, Liu L, et al. Integrins (α7β1) in muscle function and survival : disrupted expression in merosin-deficient congenital muscular dystrophy. J Clin Invest1997 ; 100 : 1870-81.
- 32. Danen EH, Sonnenberg A. Integrins in regulation of tissue development and function. J Pathol 2003 ; 201 : 632-41.
- 33. Kroemer G. Cell death and cancer : an introduction. Oncogene 2004 ; 23 : 2744-5.
- 34. Liotta AL, Kohn E. Cancer and the homeless cell. Nature 2004 ; 430 : 973-4.