An important aspect of multicellularity is that cells only grow and differentiate when in the correct context within a tissue, and remove themselves by apoptosis when they are not. Cells sense their location through specific interactions with the extracellular matrix (ECM) as well as neighbouring cells. Apoptosis in response to inappropriate cell/ECM interactions is termed anoikis, a name that in some way implies a special case of cell death initiated by signals not used in response to other proapoptotic insults.1 In practice, different cell types use diverse mechanisms to interpret signals from the ECM, all of which are found to regulate apoptosis in response to many other stimuli. The purpose of this review is to show that rather than anoikis being a specific stimulus of cell death, it is in fact a broad range of cellular responses to loss of adhesion that utilise diverse signalling and apoptotic pathways.

Anoikis is apoptosis induced by lack of correct cell/ECM attachment, and many experimental systems study this by completely detaching cells from the ECM. Some thought is required regarding the significance of anoikis in vivo. Cells in tissues require very specific ECM attachments, and the wrong type of ECM can have the same consequences as no ECM at all. The importance of anoikis in vivo can readily be seen when alterations that perturb its normal control are seen to enhance tumour metastasis, a process which requires cells to survive in totally inappropriate ECM environments.2 Anoikis, therefore, should not be considered as an experimental system in vitro, but the mechanism by which cells in vivo use ECM-derived signals to maintain tissue integrity.

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