Selective roles of integrins in the regulation of epithelial cell anoikis

整合素在上皮细胞失巢调控中的选择性作用

• 批准号: 227935-2013
• 负责人: Vachon, Pierre
• 金额: $ 2.19万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=546865
• 关键词: Selective; roles; integrins; regulation; epithelial

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.

细胞需要锚定到它们的细胞外基质才能生存。这种细胞-细胞外基质相互作用的任何扰动或损失诱导称为“失巢凋亡”（a.k.a.“凋亡诱导的细胞凋亡”，“整联蛋白介导的细胞死亡”）。失巢凋亡在组织的发育、维持和更新中起着至关重要的作用，在多细胞生物（如哺乳动物）中起着（除其他外）保险作用，因此任何偏离或逃离其锚定的细胞注定会迅速死亡，以免最终对组织和器官的正常有序功能造成问题。失巢凋亡的调节主要是由称为整合素的细胞受体制定的，整合素结合细胞外基质的组分。存在不同的整合素，其根据细胞和/或组织的类型表达。然而，整合素如何调节失巢凋亡，特别是它们发挥这种作用的信号转导，仍有待了解。因此，目前的研究计划的目的是确定和功能特征的个别整合素，在失巢凋亡的调节中发挥作用，以及这些个别整合素在失巢凋亡的调节中发挥的具体功能。我们将使用人肠上皮作为生物模型，该组织在其快速更新和根据其更新的每个步骤表达整合素方面非常了解。