Anoikis is a form of

programmed cell death Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usual ...

that occurs in anchorage-dependent cells when they detach from the surrounding

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

(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, there is a loss of normal cell–matrix interactions, and they may undergo anoikis. However,

metastatic Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

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 The ''Journal of Cell Biology'' is a peer-reviewed scientific journal published by Rockefeller University Press. History In the early 1950s, a small group of biologists began to explore intracellular anatomy using the emerging technology of e ...

'' 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 neologism construction consisting of three Greek

morpheme A morpheme is any of the smallest meaningful constituents within a linguistic expression and particularly within a word. Many words are themselves standalone morphemes, while other words contain multiple morphemes; in linguistic terminology, this ...

s agglutinated together: ἀν- "without", οἰκ- "house", and the suffix -ις.

In metastasis

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 implantation in vivo. Anisomycin achieved this anti-metastatic activity in part by decreasing the abundance of the death receptor inhibiting protein FLIP (c-Fas–associated death domain–like interleukin-1–converting enzyme–like inhibitory protein). 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. Cancer cells develop anoikis resistance by several mechanisms, including changes in integrin and matrix signaling, metabolic deregulation, and stress responses of cancer cells. One key mechanism that renders cancer cells independent from tissue adherence is dysregulation of the pathway network that controls transcription factor NF-κB.

Etymology

In metastasis

See also

References

Further reading