1003 The role of DAPK1 in the cell cycle regulation of cervical cancer cells and in response to topotecan

Introduction/Background* Cervical cancer is the fourth most common cancers among women worldwide. Primary therapy of cervical cancer depends on the disease extent and is based on radical hysterectomy or chemoradiation. However, therapeutical approaches in metastatic and recurrent disease of cervical cancer are limited. Particular effort in drug development focuses on essential serine/threonine kinases like the death-associated protein kinase 1 (DAPK1) and Polo-like kinase 1 (PLK1) as potential therapeutic targets in cervical cancer. Methodology and Result(s)* Our study examined the role of DAPK1 during the cell cycle of cervical cancer cells. We found that DAPK1 is autophosphorylated in mitosis, exhibiting only low activity towards exogenous substrates. Furthermore, DAPK1 localizes together with PLK1 at centrosomes, which can phosphorylate DAPK1. Finally, we could show that Topotecan, which is used in different clinical trials to treat cervical cancer, induces cell death, which partially depends on DAPK1. Conclusion* Topotecan is an effective drug for the treatment of cervical cancer. We explored the role of DAPK1 in Topotecan-induced cervical cancer cell death and revealed that the RNAi-based silencing of DAPK1 downregulates the apoptotic activity suggesting that DAPK1 could be a biomarker for the response to Topotecan in clinical trials.