...keratinocyte executioner named Available to Purchase

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 β1-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-β1-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...