Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma

• DOI: 10.1038/s41419-021-03919-x
• Publication Date: 2021-06-23T09:07:32Z
• Authors: Yi Zhao; Juan Yang; Jiarui Liu; Yiqing Cai; Yang Han; Shunfeng Hu; Shuai Ren; Xiangxiang Zhou; Xin Wang
• Keywords: Polo-like kinase

Abstract Polo-like kinase 4 (PLK4), a key regulator of centriole biogenesis, has recently been shown to play roles in tumorigenesis. Blocking PLK4 expression by interference or targeted drugs exhibits attractive potential improving the efficacy chemotherapy. Nevertheless, role diffuse large B-cell lymphoma (DLBCL) is still undefined. In this study, we discover that target for treatment DLBCL, and demonstrate inhibitor when used combination with doxorubicin. Pharmaceutical inhibition CFI-400945 inhibited DLBCL cell proliferation induced apoptotic death. The anti-tumor effects were accompanied mitotic defects, including polyploidy cytokinesis failure. Activation p53 Hippo/YAP tumor suppressor signaling pathway was identified as mechanisms driving activity. Moreover, resulted activation DNA damage response. Combining doxorubicin markedly delayed progression xenografts. Finally, increased primary tissues lines. High levels associated poor survival patients receiving CHOP-based treatment, implicating predictive biomarker chemosensitivity. These results provide therapeutic both monotherapy DLBCL.