Selective roles of integrins in the regulation of epithelial cell anoikis

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Cells require anchorage to their extracellular matrix in order to live. Any perturbation in, or loss of, such cell-extracellular matrix interactions induces a form of cell death that is termed "anoikis" (a.k.a. "detachment-induced apoptosis", "integrin-mediated cell death"). Anoikis performs crucial functions in development, maintenance and renewal of tissues, acting (among other things) as insurance in multi-cellular organisms (such as mammals) so that any cell which strays, or escapes, from its anchorage is fated to die quickly so as not to eventually become problematic for the proper and orderly function of tissues and organs. The regulation of anoikis is mainly enacted by cell receptors called integrins, which bind components of the extracellular matrix. Different integrins exist, which are expressed according to the type of cell and/or tissue. However, much remains to be understood as to how integrins regulate anoikis, especially with the signal transduction they enact to this effect. Consequently, the current research program aims at identifying and functionally characterizing individual integrins that perform roles in the regulation of anoikis, as well as the specific functions enacted by these individual integrins in the regulation of anoikis. We will use as biological model the human intestinal epithelium, a tissue that is very well understood with regards to its rapid renewal and its expression of integrins according to each step of its renewal.