Anoikis
Encyclopedia
Anoikis is a form of programmed cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...

 which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...

 (ECM). Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, i.e. there is a loss of normal cell–matrix interactions, they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs.

Etymology

The word Anoikis was coined by Frisch and Francis in a paper published in the Journal of Cell Biology
Journal of Cell Biology
The Journal of Cell Biology is an international, peer-reviewed journal owned by The Rockefeller University and published by The Rockefeller University Press.- History :...

 in 1994. Anoikis, in their words, means "(...the state of being without a home) to describe the cells' apoptotic response to the absence of cell–matrix interactions." The word apparently is a Neolatin construction consisting of three Greek morpheme
Morpheme
In linguistics, a morpheme is the smallest semantically meaningful unit in a language. The field of study dedicated to morphemes is called morphology. A morpheme is not identical to a word, and the principal difference between the two is that a morpheme may or may not stand alone, whereas a word,...

s agglutinated together: ἀν- "without", οἰκ- "house", and -ις (extracted from -σις "trait, attribute"; confer apo-pto-sis "state of being fallen off").

Anoikis in metastasis

The mechanism by which invading tumor cells survive the anoikis process remains largely unknown. Recent findings suggest that the protein TrkB, best known for its role in the nervous system, might be involved together with its ligand, brain-derived neurotrophic factor (BDNF). It seems that TrkB could make tumor cells resistant to anoikis by activating phosphatidylinositol 3-kinase (PI3K) signaling cascade.
In squamous cell carcinoma, researchers have found that anoikis resistance can be induced through hepatocyte growth factor (HGF) activating BOTH extracellular signalling-receptor kinase (ERK) and PI3K.

Using a novel high-throughput screening assay, Mawji et al. showed that anisomycin can sensitize metastatic epithelial cells to anoikis and reduce circulating tumor cell
Circulating Tumor Cell
Circulating tumor cells are cells that have detached from a primary tumor and circulate in the bloodstream. CTCs may constitute seeds for subsequent growth of additional tumors in different tissues....

implantation in vivo. Anisomycin achieved this anti-metastatic activity in part by decreasing the abundance of the death receptor inhibiting protein FLIP. In related work, Schimmer's team showed that FLIP levels are higher in metastatic cells than non-metastatic cells, and that reducing FLIP levels using RNAi (RNA Interference) or other small molecule inhibitors of FLIP can sensitize metastatic cells to anoikis. Given that FLIP is an inhibitor of anoikis, and that reducing FLIP can sensitize metastatic cells to anoikis, Mawji et al hypothesize that FLIP reduction may be a viable therapeutic strategy against cancer metastasis.
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