The Roles of TOPK in Tumorigenesis and Development: Structure, Mechanisms, Pathways, and Therapeutic Implications

作者：Mengyu Zhao, Min Zhang, Meng Liang, Xinru Wang, Qin Feng, Shengjie Wu, Xueli Tian, Ding Ding, Xiang Li, Kangdong Liu, Mee-Hyun Lee, Ran Zhao, Zigang Dong · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.122960 · 被引用次数：1 · 研究领域：FOXO transcription factor regulation、Mechanisms of cancer metastasis、Signaling Pathways in Disease

TOPK (T-LAK cell-originated protein kinase), also known as PDZ-binding kinase, is a serine/threonine kinase belonging to the mitogen-activated protein kinase family. It is a critical regulator of essential cellular processes, including survival, proliferation, apoptosis, inflammation, and autophagy. As an oncogenic kinase, TOPK is predominantly expressed in actively proliferating cells, where its dysregulation contributes to the pathogenesis of various cancers. Through phosphorylation, TOPK activates key signaling pathways such as ERK/RSK/c-Jun, which in turn promote cancer cell proliferation, migration, and resistance to apoptosis. Furthermore, TOPK has been implicated in the regulation of the tumor microenvironment and immune evasion. This review provides an in-depth examination of the molecular structure of TOPK, the role of TOPK in tumorigenesis, and the underlying mechanisms that support its oncogenic activity. Given its central role in cancer progression, TOPK represents a promising candidate for novel cancer therapies. Additionally, we explore the therapeutic potential of targeting TOPK in cancer treatment, highlighting ongoing research efforts and the challenges in translating TOPK inhibition into clinical practice.