HIPK2在结直肠癌中的作用研究进展
1.山东第二医科大学临床医学院，山东 潍坊 261000；
2.济南市中心医院消化内科，山东 济南 250013
收稿日期: 2025-06-25
修回日期: 2025-08-28
录用日期: 2026-03-18
网络出版日期: 2026-03-19
基金资助
山东省医药卫生科技发展计划（202003030878）；济南市科技计划（202134020）
Research Progress on the Role of HIPK2 in Colorectal Cancer
Received date: 2025-06-25
Revised date: 2025-08-28
Accepted date: 2026-03-18
Online published: 2026-03-19
结直肠癌（colorectal cancer，CRC）是全球范围内高发的消化系统恶性肿瘤之一，具有发病率高、死亡率高、复发率高的“三高”特征。目前包括手术、化疗、靶向治疗和免疫治疗在内的综合治疗手段取得了一定进展，但因其肿瘤的分子异质性及相关的易耐药性和高复发性，仍严重影响临床疗效。探索新的分子调控机制和治疗靶点已成为当前CRC基础与转化研究的核心方向。同源结构域相互作用蛋白激酶2（homeodomain-interacting protein kinase 2，HIPK2）是一种高度保守的丝氨酸/苏氨酸蛋白激酶，被认为在多种肿瘤的发生发展中发挥了关键的调控作用。HIPK2通过激活p53、调控细胞凋亡及DNA损伤修复通路，展现出显著的抑癌功能，而其表达水平的下降常与肿瘤的进展、治疗耐受及不良预后密切相关。HIPK2是一种多功能肿瘤抑制蛋白，可调节抗癌药物反应中的癌细胞生长和凋亡，并负向调节肿瘤进展和化疗耐药的途径。鉴于HIPK2在CRC发展中的关键作用，开发靶向HIPK2的小分子激动剂逐渐成为有吸引力和挑战性的热门项目。本研究从HIPK2的结构和功能、在CRC发生发展中的表达情况、对CRC细胞功能的影响以及其可能成为潜在CRC治疗靶点这几个方面加以综述。
曹宇文
,
申星杰
.
HIPK2在结直肠癌中的作用研究进展
Colorectal cancer （CRC） is one of the most common malignancies of the digestive system worldwide， characterized by high incidence， high mortality， and high recurrence. Although multimodal treatments including surgery， chemotherapy， targeted therapy， and immunotherapy have achieved certain advances， the tumor’s molecular heterogeneity， associated drug resistance， and high relapse rate still seriously compromise clinical outcomes. Therefore， identifying novel molecular regulatory mechanisms and therapeutic targets has become a central focus of basic and translational CRC research. Homeodomain-Interacting Protein Kinase 2 （HIPK2） is a highly conserved serine/threonine protein kinase that plays a key regulatory role in the development and progression of various cancers. HIPK2 exerts notable tumor-suppressive functions by activating p53 and modulating apoptosis and DNA damage-repair pathways， and its reduced expression is often closely associated with tumor progression， therapeutic resistance， and poor prognosis. As a multifunctional tumor suppressor， HIPK2 regulates cancer cell growth and apoptosis in response to anticancer agents and negatively influences pathways involved in tumor progression and chemoresistance. Given HIPK2’s pivotal role in CRC， the development of small-molecule HIPK2 agonists has emerged as an attractive yet challenging therapeutic strategy. This review summarizes HIPK2’s structure and function， its expression in CRC， its effects on CRC cell behavior， and its potential as a therapeutic target for CRC.
Key words： Colorectal cancer; HIPK2; Therapeutic target; Small molecule agonist
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