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First published online November 10, 2004

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...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.

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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] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?