PCL2 regulates p53 stability and functions as a tumor suppressor in breast cancer

Abstract

Polycomblike2 (PCL2) is a well-known component of polycomb repressive complex 2 (PRC2) and plays important roles in H3K27 methylation and homeotic gene silencing. However, the involvement of PCL2 in breast cancer development remains unclear. Here, we established PCL2 as a tumor suppressor gene in breast cancer. Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages. Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis. PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability. Mechanistically, PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus. Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition. PCL2 expression was correlated with E-cadherin expression and was inversely correlated with vimentin expression. Furthermore, PCL2 knockdown could attenuate anti-tumor effect of MLN4924. Taken together, our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.