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Genetics

An unanticipated role

Nature Reviews Cancer volume 9, page 765 (2009)Cite this article

PcG proteins can also function as tumour suppressors by repressing key oncogenic signalling pathways.

Anne-Marie Martinez, Giacomo Cavalli and colleagues generated D. melanogaster larval clones that were homozygous knockouts for the PcG polyhomeotic (ph) locus in eye imaginal discs. These imaginal discs were larger than controls, and the adults that emerged from the few surviving pupae had enlarged eyes with an abnormal morphology. Immunostaining revealed increased rates of mitosis, reduced differentiation and loss of normal polarity in the ph-null imaginal discs, indicating that ph might be a bona fide tumour suppressor. Indeed, ph clone-derived tumours could be successively retransplanted into wild-type flies in which they were able to grow and metastasize, eventually leading to death. How does loss of ph trigger tumour development? The expression of Notch , one of its ligands, Serrate ( Ser ), and a downstream effector, eyegone ( eyg ), was upregulated in ph-null cells, and the expression of all these proteins is regulated by PH. However, although overexpression of Notch in the D. melanogaster eye led to a phenotype that was similar to the loss of ph, inhibiting Notch signalling by overexpressing a dominant-negative form of Notch or by using RNA interference to repress Notch in a ph-null background produced flies with normal sized eyes but with an abnormal structure, suggesting that other PcG targets might have a role in determining the ph mutant phenotype.

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ORIGINAL RESEARCH PAPERS

  1. Martinez, A.-M. et al. Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling. Nature Genet. 13 Sep 2009 (doi: 10.1038/ng.414)

  2. Classen, A.-K. et al. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK–STAT signaling. Nature Genet. 13 Sep 2009 (doi: 10.1038/ng.445)

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Authors
  1. Meera Swami
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Swami, M. An unanticipated role. Nat Rev Cancer 9, 765 (2009). https://doi.org/10.1038/nrc2749

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