PPM1B depletion in U2OS cells supresses cell growth through RB1-E2F1 pathway and stimulates bleomycin-induced cell death.

ABSTRACT

PPM1B is a metal-dependent serine/threonine protein phosphatase, with a similar structure and function to the well-known oncogene in breast cancer, PPM1D (WIP1). However, clinical significance of PPM1B as a pharmacological target in cancer therapy has not been explored. To test if PPM1B can be a drug target in the cellular proliferation and death pathway, the lentiviral PPM1B shRNA was stably expressed in cancer cell lines and its regulatory function in the RB1-E2F1 pathway was examined. We found that PPM1B depletion suppressed cellular proliferation of U2OS cells, accompanied by hyper-phosphorylation of RB1 and up-regulation of E2F1 target genes, p27 and caspase 7. Notably, PPM1B depletion significantly sensitised U2OS cells to bleomycin-induced cell death at a minimal effective concentration. Our results suggest that PPM1B plays a negative role in the activation of the p38-RB1-E2F1 pathway and that targeting PPM1B could be useful in certain types of cancer by stimulating chemotherapy-induced cell death.