Selective roles of integrins in the regulation of epithelial cell anoikis

细胞需要锚定在细胞外基质上才能存活。这种细胞-细胞外基质相互作用的任何扰动或丧失都会导致一种称为“失巢”的细胞死亡。“脱落诱导的细胞凋亡”、“整合素介导的细胞死亡”)。Anoikis在组织的发育、维护和更新中起着至关重要的作用，在多细胞生物体(如哺乳动物)中起着保险的作用，因此任何从其锚定中迷失或逃脱的细胞注定很快就会死亡，以免最终成为组织和器官正常和有序功能的问题。失巢凋亡的调节主要是由称为整合素的细胞受体来实现的，整合素结合细胞外基质的组成部分。存在不同的整合素，它们根据细胞和/或组织的类型而表达。然而，关于整合素如何调节失巢凋亡，特别是通过它们对此影响的信号转导，仍有许多有待了解。因此，目前的研究计划旨在识别和功能表征在失巢失巢调节中发挥作用的个体整合素，以及这些个体整合素在失巢失巢调控中发挥的特定功能。我们将使用人类肠道上皮作为生物学模型，这是一种非常了解其快速更新的组织，以及根据其更新的每一步其整合素的表达。

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.