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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570345
• 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.

细胞需要固定在细胞外基质上才能生存。这种细胞-细胞外基质相互作用的任何扰动或丧失都会引起一种被称为“细胞死亡”的细胞死亡形式。“分离诱导的细胞凋亡”，“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）中起着保险作用（以及其他作用），这样，任何偏离或逃离其锚点的细胞都注定会迅速死亡，从而最终不会对组织和器官的正常有序功能造成问题。anoikis的调节主要是由称为整合素的细胞受体实施的，整合素结合细胞外基质的成分。存在不同的整合素，它们根据细胞和/或组织的类型表达。然而，关于整合素如何调节anoikis，特别是它们如何发挥这种作用的信号转导，还有很多有待了解的地方。因此，目前的研究计划旨在识别和功能表征在anoikis调节中发挥作用的个体整合素，以及这些个体整合素在anoikis调节中所发挥的特定功能。我们将使用人类肠上皮作为生物学模型，肠上皮是一种组织，它的快速更新和根据其更新的每一步整合素的表达是非常清楚的。