Loss of the Polycomb group gene polyhomeotic induces non-autonomous cell overproliferation

Polycomb group (PcG) proteins are conserved epigenetic regulators that are linked to cancer in humans. However, little is known about how they control cell proliferation. Here, we report that mutant clones of the PcG gene polyhomeotic (ph) form unique single-cell-layer cavities that secrete three JAK/STAT pathway ligands, which in turn act redundantly to stimulate overproliferation of surrounding wild-type cells. Notably, different ph alleles cause different phenotypes at the cellular level. Although the ph-null allele induces non-autonomous overgrowth, an allele encoding truncated Ph induces both autonomous and non-autonomous overgrowth. We propose that PcG misregulation promotes tumorigenesis through several cellular mechanisms.