Till Death Us Do Part

New work that identifies the trigger that sets in motion the apoptosis program following detachment is discussed, and the trigger turns out to be the pro-apoptotic protein Bmf.

Abstract

T he wonder of multicellular organisms is that each individual cell seems to know what to do, where to be, and how to behave. Such remarkable self-organization relies in part on the surprising alacrity of cells to commit suicide, a process termed apoptosis, should they stray or be misplaced from their normal somatic compartment and so become deprived of the requisite social signals needed for their survival. Nowhere is this phenomenon more evident than in epithelial cells, which derive much of their positional information from their association with their neighbors and with the extracellular matrix. Deprived of such associations, epithelial cells typically undergo detachment-induced apoptosis, or anoikis. Such spontaneous suicide effectively confines epithelial tissues to their correct somatic compartments, ensuring the expeditious deletion of cells misplaced during development or through injury, and potently restraining the emergence of invasive malignancies. Accordingly, inactivation of anoikis is a critical step in the progression of epithelial cancers to an invasive and metastatic form. On page 1829 of this issue, Puthalakath et al. (1) show that detachment of epithelial cells from their extracellular matrix detonates an apoptotic bomb by triggering the release of the pro-apoptotic protein Bmf from the myosin V motor complex of the actin cytoskeleton.