Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications.
分化簇44（CD44）是一种非激酶细胞表面糖蛋白，在包括癌症干细胞（CSCs）在内的多种细胞类型中过度表达。过度表达CD44的细胞表现出多种癌症干细胞特性，如自我更新、上皮-间质转化（EMT）能力以及对化疗和放疗的抵抗性。CD44通过与其主要配体透明质酸（HA）结合，在维持干细胞特性及癌症干细胞功能促进肿瘤进展中发挥关键作用。HA-CD44复合物可激活多种信号通路，进而促进细胞增殖、黏附、迁移和侵袭。CD44基因经常发生选择性剪接，产生标准型（CD44s）和变异型（CD44v）亚型。目前对CD44s及特定CD44v亚型的不同功能角色尚未完全阐明。CD44及其亚型在促进肿瘤发生发展中的临床病理学影响表明，CD44可能成为癌症治疗的分子靶点。此外，近期研究发现CD44与KRAS依赖性癌之间存在关联，且CD44与肿瘤突变负荷（TMB）及微卫星不稳定性（MSI）存在潜在相关性，这为开发癌症治疗新策略开辟了新的研究方向。本综述总结了当前关于不同CD44亚型结构及其在支持肿瘤发生发展中的作用与功能的研究进展，并探讨了其治疗意义。
肿瘤(癌症)患者之家