Vachon Pierre H
Groupe IRSC, Développement Fonctionnel et Physiopathologie du Tractus Digestif, Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Québec, Canada.
Med Sci (Paris). 2006 Apr;22(4):423-9. doi: 10.1051/medsci/2006224423.
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.
细胞存活与凋亡的调控机制本质上非常复杂,涉及众多参与者和信号通路,不仅在存活(或死亡)的决策过程中如此,在凋亡的执行过程中也是如此。这种复杂的本质同样适用于失巢凋亡,它是一种主要由整合素介导的细胞与细胞外基质相互作用调控的凋亡形式。然而,根据所涉及的特定组织和/或细胞类型,细胞存活、凋亡和失巢凋亡在机制上也存在进一步的差异。顺便提一下,最近在一种特定组织——人类肠上皮中的研究,揭示了这三种细胞过程调控中又一层复杂性,即分化状态特异性机制的作用。尽管我们对细胞存活、凋亡和/或失巢凋亡的这种分化状态特异性调控新概念的分子基础的理解尚处于起步阶段,但已有证据表明,这一原理也适用于肠上皮细胞以外的其他细胞类型。在正常或病理生理情况下,对这三种细胞过程的分化状态特异性调控进行进一步研究,对于加深我们对涉及凋亡和/或失巢凋亡失调的疾病(如癌症)的理解至关重要。