First published online November 10, 2004
Journal of Cell Science 117, 2404e (2004)
© The Company of Biologists Limited
...keratinocyte executioner named
Anoikis – apoptosis induced by detachment of cells from the extracellular matrix – is common in many adherent cells, including keratinocytes. Given its importance for normal tissue homeostasis and its disruption in metastasizing tumour cells, establishing the molecular mechanisms driving anoikis is an important goal. Alessandra Marconi and co-workers have therefore examined how loss of ß1-integrin attachment induces anoikis in keratinocyte stem cells and transit amplifying (TA) cells (see p. 5815). They find that the apoptotic protease caspase-8 (an `initiator' caspase) is activated following induction of anoikis by neutralizing anti-ß1-integrin antibodies. This implicates the `extrinsic', death-receptor-activated pathway rather than the `intrinsic', stress-activated pathway of apoptosis. The authors provide further supporting evidence by demonstrating that the caspase-8 inhibitor zIETD-fmk blocks anoikis in keratinocytes and can inhibit downstream apoptotic events such as activation of `executioner' caspases (e.g. caspase-3). Moreover, they show that overexpression of FLIP – an endogenous molecule that inhibits caspase-8 processing – can also prevent anoikis. Interestingly, activation of caspase-8 is much faster in TA cells (which are committed to differentiation) than keratinocyte stem cells – possibly because TA cells have lower levels of ß1-integrin and therefore reduced survival signalling to overcome.
Related articles in JCS:
- FLICE/caspase-8 activation triggers anoikis induced by ß1-integrin blockade in human keratinocytes
- Alessandra Marconi, Paola Atzei, Cristina Panza, Chiara Fila, Rossana Tiberio, Francesca Truzzi, Tina Wachter, Martin Leverkus, and Carlo Pincelli
JCS 2004 117: 5815-5823.
[Abstract]
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