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Citation
Classen, A.K., Bunker, B.D., Harvey, K.F., Vaccari, T., Bilder, D. (2009). A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling.  Nat. Genet. 41(10): 1150--1155.
FlyBase ID
FBrf0208982
Publication Type
Research paper
Abstract

A prevailing paradigm posits that Polycomb Group (PcG) proteins maintain stem cell identity by repressing differentiation genes, and abundant evidence points to an oncogenic role for PcG proteins in human cancer. Here we show using Drosophila melanogaster that a conventional PcG complex can also have a potent tumor suppressor activity. Mutations in any core PRC1 component cause pronounced hyperproliferation of eye imaginal tissue, accompanied by deregulation of epithelial architecture. The mitogenic JAK-STAT pathway is strongly and specifically activated in mutant tissue; activation is driven by transcriptional upregulation of Unpaired (Upd, also known as Outstretched, Os) family ligands. We show here that upd genes are direct targets of PcG-mediated repression in imaginal discs. Ectopic JAK-STAT activity is sufficient to induce overproliferation, whereas reduction of JAK-STAT activity suppresses the PRC1 mutant tumor phenotype. These findings show that PcG proteins can restrict growth directly by silencing mitogenic signaling pathways, shedding light on an epigenetic mechanism underlying tumor suppression.

PubMed ID
PubMed Central ID
PMC2782793 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Genet.
    Title
    Nature Genetics
    Publication Year
    1992-
    ISBN/ISSN
    1061-4036 1546-1718
    Data From Reference
    Aberrations (2)
    Alleles (15)
    Genes (32)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (3)