|
Cancer Glossary & Scientific Reference:
Anoikis
Anoikis
by Steven M. Frisch, The Burnham Institute, La Jolla, CA, USA , sfrisch at burnham-inst.org
Definition
Anoikis is the apoptosis of cells that have lost contact with extracellular matrix, or that interact with matrix through an inappropriate integrin-matrix combination.
Characteristics
Documented to occur in epithelial, endothelial, muscle cells and
oligodendrocytes; also occurs in fibroblasts subjected to growth
factor deprivation, possibly by different mechanisms;
occurs through established apoptotic signaling pathways, which
depend upon cell type. These include caspases of both the initiator
(caspase-8) and effector (caspase-3,7) types as well as protein
kinases such as MEKK- 1/JNK; protection against anoikis is
afforded by the activation of certain other kinases such as FAK and
Akt. Bcl-2/Bcl-xL involvement depends upon cell type;
in certain epithelial cell lines, cells must achieve complete cell-cell
contact while attached to matrix, to become sensitive to anoikis;
transformation by oncogenes or loss of tumor suppressor genes
can render tumor cells resistant to anoikis, promoting anchorage
independent growth/metastasis.
Cellular and molecular aspects
Cells undergoing anoikis-typical apoptotic characteristics:
nucleosomal DNA ladder formation, cell shrinkage, caspase
activation/cleavage of caspase substrates, cytochrome c release
from mitochondria;
anoikis is defined operationally, so whether a cell dies from
cell-matrix dissociation or from another stimulus can only be
determined experimentally, not retrospectively in vivo.
Clinical relevance
Anoikis is thought to be relevant to normal tissue homeostasis of
rapid turnover epithelial tissues such as in the digestive tract. It is
also important for embryonic development (gastrulation) and
mammary gland involution;
sensitivity to anoikis is frequently lost in tumor cells, which
probably contributes to their ability to grow independently of
anchorage, and metastasize. It is also involved in muscle
degeneration in muscular dystrophy;
this sensitivity can be lost by activated oncogenes such as ras,
alterations in intracellular apoptosis components, overexpression
of growth factors such as EGF, HGF or IGF-related molecules, or
breakdown of cadherincatenin complexes.
References
1. Frisch, S.M. and Ruoslahti, E (1997). Integrins and anoikis. Curr. Opin. Cell Biol. 9:
701-706
2. Frisch, S.M. and Francis, H (1994). Disruption of epithelial cell-matrix interactions
induces apoptosis. J. Cell Biol. 124: 619-626
3. Aplin A., Howe A, Juliano R (1999). Cell adhesion molecules, signal transduction
and cell growth. Curr. Opin. Cell Biol. 11: 737-744
4. Ashkenazi A, Dixit V (1999). Apoptosis control by death and
decoy receptors. Curr. Opin. Cell Biol. 11: 255-260
5. Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M, Lord JM (2000).
Serine/threonine protein kinases and apoptosis. Experimental Cell Research 256:
34-41
6. Bratton SB, MacFarlane M, Cain K, Cohen GM (2000) Protein complexes activate
distinct caspase cascades in death receptor and stress-induced apoptosis.
Experimental Cell Research 256: 27-33
For the main subject of this site, the holistic healing of cancer, refer to Healing Cancer Naturally & any of the menu points listed at the bottom & top of most pages.
Click here for overview over the complete
cancer glossary & scientific reference section featured at Healing Cancer Naturally.
go to top
|
|
