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Anoikis (detachment induced cell death or suspension induced apoptosis) is the name given to a special form of cell death by apoptosis. It was observed initially after disruption of the interactions between normal epithelial cells and extracellular matrix. In an intact organism anoikis ensures that cells are unable to survive in an inappropriate location. Anoikis thus is apoptosis caused by cell isolation or apoptosis of cells in suspension or, generally speaking, apoptosis caused by loss of adherence to substrate.
Detachment induced cell death can interfere with the establishment of long-term primary cultures of human epithelial cells as the cells may die during isolation. Grossmann et al (1998) have described a protocol for the isolation of highly purified human colonic epithelial cells from surgical specimens facilitating the establishment of such primary cell cultures.
The molecular mechanisms underlying anoikis have not been elucidated in detail. Cell death by anoikis is not seen in epithelial cells transformed with oncogenic DNA or RNA tumor viruses or after treatment with phorbol esters. Anoikis in MDCK cells has been shown to be alleviated by the cell motility factor SF (scatter factor), suggesting that the process can be circumvented by the acquisition of anchorage independence (see also: Anchorage-dependent cells, Cell culture), or cell motility (see also: Motogenic cytokines). The aberrant expression of an oncogene or tumor suppressor gene can cause resistance to anoikis, thereby contributing substantially to malignancy.
The expression of some genes involved in cell death, for example TRAIL, has been shown to be suppressed by anchorage and this may provide a mechanism to prevent apoptosis of cells that would otherwise experience anoikis.
Withdrawal of serum, growth factors or cytokines can cause this type of cell death and some cytokines can prevent cell death by anoikis. IGF-1, for example protects mouse embryo fibroblasts from anoikis.
Among other things the process of anoikis involves cellular integrins and components of the extracellular matrix, including matrix metalloproteinases. Protein kinase signaling pathways control anoikis both positively and negatively and the expression of at least one integrin-interacting protein (integrin-linked kinase, ILK) has been shown to be stimulated upon adhesion of epithelial cells and to be inhibited in suspended cells while its overexpression in anoikis-sensitive cells results in a profound inhibition of anoikis.
Some components of the apoptosis death pathway (BCL2 and BCLxL, for example, and a variety of death receptor proteins or proteins containing a death domain) are involved also. TFF-3 (trefoil factor-2), a peptide secreted by intestinal goblet cells, has been shown to induce resistance to anoikis.
Giannoni E et al (2008) have demonstrated that reactive oxygen species produced through the involvement of the small GTPase Rac-1 upon integrin engagement exert a mandatory role in transducing a pro-survival signal that ensures that cells escape from anoikis. This process involves the redox-mediated activation of Src that trans-phosphorylates the EGF receptor in a ligand-independent manner and eventually the degradation of the pro-apoptotic protein BIM.
Some viral genomes appear to encode proteins (HIV vpr protein) that maintain cell survival by inducing anoikis resistance.
Some proteins widely used as tumor markers, such as human carcinoembryonic antigen (CEA), are upregulated in many types of human cancers and have been shown to inhibit apoptotic cell death by anoikis. These proteins may promote metastatic processes by blocking the tissue architecture surveillance mechanism monitoring adherence and anchorage to their substrates.
For other entries pertaining to cell death mechanisms see also the Apoptosis and Cell Death Dictionary section of this encyclopedia. For other related/relevant entries see also: Cell types.
Copyright © 2012 by H IBELGAUFTS. All rights reserved.
ENTRY LAST MODIFIED: August 2008
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