Biology:Anoikis
Anoikis is a form of programmed cell death that occurs in anchorage-dependent cells when they detach from the surrounding extracellular matrix (ECM).[1] 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 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 in 1994.[2] "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 morphemes agglutinated together: ἀν- "without", οἰκ- "house", and the suffix -ις.
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) [citation needed]. It seems that TrkB could make tumor cells resistant to anoikis by activating phosphatidylinositol 3-kinase (PI3K) signaling cascade [citation needed]. 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 [citation needed].
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.[3] 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.[4] 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.[5] One key mechanism that renders cancer cells independent from tissue adherence is dysregulation of the pathway network that controls transcription factor NF-κB.
See also
References
- ↑ "Anoikis mechanisms". Current Opinion in Cell Biology 13 (5): 555–62. October 2001. doi:10.1016/S0955-0674(00)00251-9. PMID 11544023.
- ↑ Frisch, SM.; Francis, H. (Feb 1994). "Disruption of epithelial cell-matrix interactions induces apoptosis.". J Cell Biol 124 (4): 619–26. doi:10.1083/jcb.124.4.619. PMID 8106557.
- ↑ "A chemical screen identifies anisomycin as an anoikis sensitizer that functions by decreasing FLIP protein synthesis". Cancer Research 67 (17): 8307–15. September 2007. doi:10.1158/0008-5472.CAN-07-1687. PMID 17804746.
- ↑ "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 99 (10): 811–22. May 2007. doi:10.1093/jnci/djk182. PMID 17505076.
- ↑ "Anoikis molecular pathways and its role in cancer progression.". Biochim Biophys Acta 1833 (12): 3481–3498. 2013. doi:10.1016/j.bbamcr.2013.06.026. PMID 23830918.
Further reading
- "Anoikis: cancer and the homeless cell". Nature 430 (7003): 973–4. August 2004. doi:10.1038/430973a. PMID 15329701.
- "Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B". The Journal of Biological Chemistry 277 (28): 25203–8. July 2002. doi:10.1074/jbc.M201598200. PMID 11994287.
- Vlahopoulos, SA (August 2017). "Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode.". Cancer Biology & Medicine 14 (3): 254–270. doi:10.20892/j.issn.2095-3941.2017.0029. PMID 28884042.
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