The role of human pygopus 2 in the proliferation of ovarian cancer cells

Abstract

Pygopus plays an important role in canonical Wnt signaling by functioning in complex with T cell Factor (TCF), b Cell Lymphoma 9 (BCL9) and β-catenin to activate target gene transcription. Many cancers show mutational defects in components of the Wnt pathway, leading to β-catenin overexpression and increased TCF-mediated transcription of the target genes. Pygopus is crucial to this target gene overexpression in that it is a required protein in the transcription complex. As such, we show pygopus is overexpressed in Epithelial Ovarian Cancer (EOC) cell lines and is required for their proliferation. To date pygopus function has only been studied in relation to its canonical Wnt signaling activity. However, we also demonstrate that pygopus functions outside the canonical Wnt pathway as a transactivator and that its presence is required for EOC proliferation regardless of whether it functions in the canonical Wnt signaling pathway.