PBK/TOPK: A Therapeutic Target Worthy of Attention
Ziping Han1, Lingzhi Li1, Yuyou Huang1
1Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
Abstract:
Accumulating evidence supports the role of PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies. Therefore, it is a potential therapeutic target in cancer therapy. Many studies have been conducted to explore the clinical applicability of potent PBK/TOPK inhibitors. However, PBK/TOPK has also been shown to be overexpressed in normal proliferative cells, including sperm and neural precursor cells in the subventricular zone of the adult brain, as well as under pathological conditions, such as ischemic tissues, including the heart, brain, and kidney, and plays important roles in their physiological functions, including proliferation and self-renewal. Thus, more research is warranted to further our understanding of PBK/TOPK inhibitors before we can consider their applicability in clinical practice. In this study, we first review the findings, general features, and signaling mechanisms involved in the regulation of mitosis and cell cycle. We then review the functions of PBK/TOPK in pathological conditions, including tumors and ischemic conditions in the heart, brain, and kidney. Finally, we summarize the advances in potent and selective inhibitors and describe the potential use of PBK/TOPK inhibitors in clinical settings.
Insights
PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) is crucial for cell division and cancer progression. Further research on PBK/TOPK inhibitors is needed due to its role in normal tissues.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) plays a key role in mitosis and cell cycle regulation.
- PBK/TOPK is implicated in the development, progression, and metastasis of various malignancies, making it a potential cancer therapeutic target.
- PBK/TOPK is also expressed in normal proliferative cells and under pathological conditions like ischemia, highlighting its complex physiological roles.
Purpose of the Study:
- To review the general features, signaling mechanisms, and mitotic roles of PBK/TOPK.
- To examine the functions of PBK/TOPK in pathological conditions, including tumors and ischemic tissues.
- To summarize advancements in PBK/TOPK inhibitors and discuss their potential clinical applications.
Main Methods:
- Literature review of existing studies on PBK/TOPK.
- Analysis of PBK/TOPK's role in cell cycle regulation and cancer.
- Review of current research on PBK/TOPK inhibitors and their therapeutic potential.
Main Results:
- PBK/TOPK is integral to mitosis and cell proliferation, particularly in malignant cells.
- PBK/TOPK's involvement extends to normal cell functions and pathological conditions like ischemia.
- Development of potent and selective PBK/TOPK inhibitors is ongoing, showing promise for therapeutic use.
Conclusions:
- PBK/TOPK is a significant target for cancer therapy due to its role in malignancy.
- The dual role of PBK/TOPK in both cancer and normal tissues necessitates careful consideration for inhibitor development.
- Further research is essential to fully understand PBK/TOPK inhibitors' clinical applicability and ensure safety.
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