Anoikis is a form of

programmed cell death Programmed cell death (PCD; sometimes referred to as 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 usually confers ...

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

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

(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 spread 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, then, ...

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 ele ...

'' 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 the smallest meaningful constituent of a linguistic expression. The field of linguistic study dedicated to morphemes is called morphology. In English, morphemes are often but not necessarily words. Morphemes that stand alone are ...

s agglutinated together: ἀν- "without", οἰκ- "house", and the suffix -ις. Unfortunately, for a Greek native speaker that does not make sense, because in Greek the state of being without a home is described by the word "αστεγος", pronounced "astegos". Furthermore, "anoikis" is pronounced exactly the same way as the Greek word "ανήκεις", which means "you belong", adding to the confusion.

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 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. 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