Squeezed to death: Mechanical control of MLKL beyond RIPK3.

Prolonged confinement is a consequence of amoeboid cancer-cell invasion. In this issue of Developmental Cell, Zhang et al.1 show that sustained mechanical stress activates PIEZO1-STAT1-dependent MLKL expression, leading to MLKL-dependent membrane-lytic death in cells without detectable RIPK3 and canonical MLKL phosphorylation, broadening current models of necroptotic competence.