Anoikis

Etymology

The word "anoikis" was coined by Frisch and Francis in a paper published in the Journal of Cell Biology 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 is a neologism construction consisting of three Greek morphemes 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.

References

References

1. (October 2001). "Anoikis mechanisms". Current Opinion in Cell Biology.
2. (Feb 1994). "Disruption of epithelial cell-matrix interactions induces apoptosis.". J Cell Biol.
3. (September 2007). "A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis". Cancer Research.
4. (May 2007). "Critical role for Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein in anoikis resistance and distant tumor formation". Journal of the National Cancer Institute.
5. (2013). "Anoikis molecular pathways and its role in cancer progression.". Biochim Biophys Acta.