Xu Hanxiao, Niu Mengke, Yuan Xun, Wu Kongming, Liu Aiguo
Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Medical Oncology, The Affiliated Tumor Hospital of Zhengzhou University: Henan Cancer Hospital, Zhengzhou, 450008, China.
Exp Hematol Oncol. 2020 Dec 10;9(1):36. doi: 10.1186/s40164-020-00192-0.
CD44, a complex transmembrane glycoprotein, exists in multiple molecular forms, including the standard isoform CD44s and CD44 variant isoforms. CD44 participates in multiple physiological processes, and aberrant expression and dysregulation of CD44 contribute to tumor initiation and progression. CD44 represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is involved in the regulation of diverse vital signaling pathways that modulate cancer proliferation, invasion, metastasis and therapy-resistance, and it is also modulated by a variety of molecules in cancer cells. In addition, CD44 can serve as an adverse prognostic marker among cancer population. The pleiotropic roles of CD44 in carcinoma potentially offering new molecular target for therapeutic intervention. Preclinical and clinical trials for evaluating the pharmacokinetics, efficacy and drug-related toxicity of CD44 monoclonal antibody have been carried out among tumors with CD44 expression. In this review, we focus on current data relevant to CD44, and outline CD44 structure, the regulation of CD44, functional properties of CD44 in carcinogenesis and cancer progression as well as the potential CD44-targeting therapy for cancer management.
CD44是一种复杂的跨膜糖蛋白，以多种分子形式存在，包括标准异构体CD44s和CD44变异异构体。CD44参与多种生理过程，CD44的异常表达和失调有助于肿瘤的发生和进展。CD44是癌症干细胞的常见生物标志物，并促进上皮-间质转化。CD44参与调节多种重要的信号通路，这些信号通路调节癌症的增殖、侵袭、转移和治疗抗性，并且它也受到癌细胞中多种分子的调节。此外，CD44可作为癌症人群中的不良预后标志物。CD44在癌症中的多效性作用可能为治疗干预提供新的分子靶点。针对表达CD44的肿瘤，已经开展了评估CD44单克隆抗体的药代动力学、疗效和药物相关毒性的临床前和临床试验。在本综述中，我们关注与CD44相关的当前数据，并概述CD44的结构、CD44的调节、CD44在致癌作用和癌症进展中的功能特性以及针对癌症治疗的潜在CD44靶向疗法。
