Shen Xinzhuang, Luo Dehong, Yang Xiaowen, Li Yifei, Lian Fuming, Liu Huan, Zhang Xiaoyuan, Shen Wenzhi
College of Clinical Medicine, Jining Medical University, Jining 272067, China.
Shandong Provincial Precision Medicine Laboratory for Chronic Non-communicable Diseases, Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
J Cancer. 2025 Jan 27;16(5):1563-1574. doi: 10.7150/jca.100612. eCollection 2025.
The intercellular adhesion molecule 3 (ICAM3), also known as CD50, is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins containing 2-9 immunoglobulin-like C2-type structural domains and bind to the lymphocyte function-associated antigen-1 (LFA-1) protein. ICAM3 is abundantly and constitutively expressed in all leukocytes and is probably the most important ligand for LFA-1 in initiating immune responses. In recent years, more and more studies have focused on ICAM3 and found that it is closely related to the pathogenesis of various diseases. Here, we summarize the genomic localization, protein structure, and basic functions of ICAM3, and discuss the research progress of ICAM3 in mediating immune cell function and other diseases. Further, we describe the regulatory role of ICAM3 on the progression of different types of malignant cancers and the associated signaling pathways. Our work assesses the feasibility of ICAM3 as a molecular marker for the diagnosis of human diseases and cancers, which may provide new targets for treating related diseases and cancers. As a typical transmembrane protein, we expect to find or synthesize specific small molecule inhibitors for the treatment of clinically relevant diseases.
细胞间黏附分子3(ICAM3),也称为CD50,是细胞间黏附分子(ICAM)家族的成员。所有ICAM蛋白都是I型跨膜糖蛋白,含有2 - 9个免疫球蛋白样C2型结构域,并与淋巴细胞功能相关抗原-1(LFA-1)蛋白结合。ICAM3在所有白细胞中大量组成性表达,可能是启动免疫反应时LFA-1最重要的配体。近年来,越来越多的研究聚焦于ICAM3,并发现它与多种疾病的发病机制密切相关。在此,我们总结ICAM3的基因组定位、蛋白质结构和基本功能,并讨论ICAM3在介导免疫细胞功能及其他疾病方面的研究进展。此外,我们描述ICAM3对不同类型恶性肿瘤进展的调节作用及相关信号通路。我们的工作评估了ICAM3作为人类疾病和癌症诊断分子标志物的可行性,这可能为治疗相关疾病和癌症提供新靶点。作为一种典型的跨膜蛋白,我们期望找到或合成用于治疗临床相关疾病的特异性小分子抑制剂。