Context-dependent actions of Polycomb repressors in cancer

Polycomb Group (PcG) proteins form Polycomb Repressive Complexes (PRCs) that function as epigenetic repressors of gene expression. The large variety of PcG proteins, in addition to the high number of paralogs, allows for the formation of diverse PRCs with different properties, providing fine-tuned control over cell specification. Initially identified as being oncogenes, a small number of PcG genes are involved in tumor development in part through the repression of the CDKN2A locus. Therefore, enhanced PcG-mediated repression has long been assumed to be cancer promoting. However, recent data have revealed that for some cancers, PcG proteins act as tumor suppressors, indicating that this traditional view is oversimplified. In this review, we present an overview of the roles of PcG genes in oncogenesis and how the nature of their role is context dependent.