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TOPK 在肿瘤发生与发展中的作用:结构、机制、通路及治疗意义

英文原题:The Roles of TOPK in Tumorigenesis and Development: Structure, Mechanisms, Pathways, and Therapeutic Implications.

查看英文原题

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

PubMed 2026/01/01(内容时间) Int J Biol Sci Q1 · IF 11.7(JCR 2025)

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中文摘要

TOPK(T-LAK细胞起源的蛋白激酶),也称为PDZ结合激酶,是一种属于丝裂原活化蛋白激酶家族的丝氨酸/苏氨酸激酶。它是细胞存活、增殖、凋亡、炎症和自噬等基本细胞过程的关键调控因子。作为一种致癌激酶,TOPK主要在活跃增殖的细胞中表达,其失调促进了多种癌症的发病机制。通过磷酸化作用,TOPK激活ERK/RSK/c-Jun等关键信号通路,进而促进癌细胞增殖、迁移和抗凋亡能力。此外,TOPK还参与肿瘤微环境的调控和免疫逃逸。本综述深入探讨了TOPK的分子结构、TOPK在肿瘤发生中的作用以及支持其致癌活性的潜在机制。鉴于TOPK在癌症进展中的核心作用,它代表了新型癌症疗法的有前景的候选靶点。此外,我们探讨了靶向TOPK在癌症治疗中的治疗潜力,重点介绍了正在进行的研究工作以及将TOPK抑制转化为临床实践所面临的挑战。

展开英文摘要原文

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.

论文信息

作者
Zhao M、Zhang M、Liang M、Wang X、Feng Q、Wu S、Tian X、Ding D
单位
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.China
文献类型
综述
期刊
International journal of biological sciences2026
原文标识
PubMed 41362722 · DOI 10.7150/ijbs.122960