LAUSR

Animals have evolved mechanisms, such as cell competition, to remove dangerous or nonfunctional cells from a tissue. Tumor necrosis factor signaling can eliminate clonal malignancies from Drosophila imaginal epithelia, but why this pathway is activated in tumor cells but not normal tissue is unknown. We show that the ligand that drives elimination is present in basolateral circulation but remains latent because it is spatially segregated from its apically localized receptor. Polarity defects associated with malignant transformation cause receptor mislocalization, allowing ligand binding and subsequent apoptotic signaling. This process occurs irrespective of the neighboring cells’ genotype and is thus distinct from cell competition. Related phenomena at epithelial wound sites are required for efficient repair. This mechanism of polarized compartmentalization of ligand and receptor can generally monitor epithelial integrity to promote tissue homeostasis. Description Monitoring epithelial integrity Epithelia provide protective interfaces between various tissues and their surrounding environment. To function as barriers, epithelia must surveil themselves to prevent breaches that can be caused by either physical damage or the formation of aberrant cells. The mechanism by which an epithelium monitors and maintains its integrity is largely unknown. De Vreede et al. describe a signaling system in fruit fly organs in which an apically polarized receptor is spatially compartmentalized away from its ligand that circulates in the basal milieu. Polarity defects common to neoplastic cells or wounds mislocalize the receptor, allowing ligand binding and signal transduction. This work shows how an elegant mechanism that detects and repairs breaches to the epithelial barrier has also been adopted to eliminate oncogenic clones and explains how epithelial defects can be recognized as a damage-associated molecular pattern. —BAP Transformed cells and wounds activate a polarity-enforced latent signaling system to trigger either cell death or wound repair in fruit flies.