Related Experiment Video
Updated: Aug 5, 2026
MISSION LentiPlex Pooled shRNA Library Screening in Mammalian Cells
Published on: December 21, 2011
Kinome-wide CRISPR-Cas9 knockout screens revealed PLK1 as a therapeutic target for osteosarcoma
Renxian Wang1, Dingding Wang2, Xueshan Bai3
1Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Abstract:
Osteosarcoma is the most common malignant bone tumor, tending to be aggressive and recurrent. The therapeutic development for treating osteosarcoma has been largely hampered by the lack of effective and specific targets. Using kinome-wide CRISPR-Cas9 knockout screens, we systematically revealed a cohort of kinases essential for the survival and growth of human osteosarcoma cells, in which Polo-like kinase 1 (PLK1) appeared as a specific prominent hit. PLK1 knockout substantially inhibited proliferation of osteosarcoma cells in vitro and the tumor growth of osteosarcoma xenograft in vivo. Volasertib, a potent experimental PLK1 inhibitor, can effectively inhibit the growth of the osteosarcoma cell lines in vitro. It can also disrupt the development of tumors in the patient-derived xenograft (PDX) models in vivo. Furthermore, we confirmed that the mode of action (MoA) of volasertib is primarily mediated by the cell-cycle arrest and apoptosis triggered by DNA damage. As PLK1 inhibitors are entering phase III clinical trials, our findings provide important insights into the efficacy and MoA of the relevant therapeutic approach for combating osteosarcoma.
Insights
Researchers identified Polo-like kinase 1 (PLK1) as a key target for osteosarcoma. Inhibiting PLK1 with volasertib effectively stops cancer growth and triggers cell death, offering a promising new therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma is the most common aggressive bone cancer with limited effective therapeutic targets.
- Developing specific and effective treatments for osteosarcoma remains a significant challenge.
Purpose of the Study:
- To identify novel therapeutic targets in osteosarcoma using kinome-wide screening.
- To evaluate the efficacy and mechanism of action of Polo-like kinase 1 (PLK1) inhibition in osteosarcoma.
Main Methods:
- Utilized kinome-wide CRISPR-Cas9 knockout screens to identify essential kinases in osteosarcoma cells.
- Assessed the impact of PLK1 knockout and volasertib (a PLK1 inhibitor) on osteosarcoma cell proliferation and tumor growth in vitro and in vivo (xenograft and patient-derived xenograft models).
- Investigated the mechanism of action of volasertib, focusing on cell-cycle arrest, apoptosis, and DNA damage.
Main Results:
- PLK1 was identified as a crucial kinase for osteosarcoma cell survival and growth.
- PLK1 knockout significantly inhibited osteosarcoma cell proliferation and tumor growth in vivo.
- Volasertib demonstrated potent inhibition of osteosarcoma cell lines and disrupted tumor development in patient-derived xenograft models.
- Volasertib's mechanism involves inducing cell-cycle arrest and apoptosis through DNA damage.
Conclusions:
- PLK1 is a specific and effective therapeutic target for osteosarcoma.
- Volasertib shows significant potential as an anti-osteosarcoma agent, acting via cell-cycle arrest and apoptosis.
- These findings support the clinical investigation of PLK1 inhibitors for osteosarcoma treatment.
