CD44: A Multifunctional Mediator of Cancer Progression.
CD44: A Multifunctional Mediator of Cancer Progression.
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DOI：
10.3390/biom11121850
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发表时间：
2021-12-09
期刊：
影响因子：
5.5
通讯作者：
Syahir A
中科院分区：
文献类型：
--
作者：
Hassn Mesrati M;Syafruddin SE;Mohtar MA;Syahir A
CD 44是一种非激酶细胞表面跨膜糖蛋白，已被广泛认为是几种癌症中的癌症干细胞（CSC）标志物。过表达CD 44的细胞具有几种CSC特征，如自我更新和上皮-间质转化（EMT）能力，以及对化疗和放疗的抗性。CD 44基因有规律地进行选择性剪接，产生标准（CD 44 s）和变体（CD 44 v）同种型。这些亚型与配体，特别是透明质酸（HA），骨桥蛋白（OPN）和基质金属蛋白酶（MMP）的相互作用，驱动许多癌症相关的信号传导。然而，关于高或低CD 44表达是否与恶化的临床病理特征相关，如较高的肿瘤组织学分级，晚期肿瘤分期和较差的生存率，存在相互矛盾的结果。尽管如此，高CD 44表达显著有助于增强肿瘤发生机制，如细胞增殖、转移、侵袭、迁移和干性;因此，CD 44是重要的临床靶点。本文综述了目前的研究，不同的CD 44亚型的结构和它们的作用和功能，在支持肿瘤的发生，并讨论了CD 44的表达调控，CD 44信号通路和相互作用参与癌症的发展。CD 44的临床意义和预后价值以及CD 44作为癌症治疗靶点的潜力也得到了解决。
CD44, a non-kinase cell surface transmembrane glycoprotein, has been widely implicated as a cancer stem cell (CSC) marker in several cancers. Cells overexpressing CD44 possess several CSC traits, such as self-renewal and epithelial-mesenchymal transition (EMT) capability, as well as a resistance to chemo- and radiotherapy. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The interaction of such isoforms with ligands, particularly hyaluronic acid (HA), osteopontin (OPN) and matrix metalloproteinases (MMPs), drive numerous cancer-associated signalling. However, there are contradictory results regarding whether high or low CD44 expression is associated with worsening clinicopathological features, such as a higher tumour histological grade, advanced tumour stage and poorer survival rates. Nonetheless, high CD44 expression significantly contributes to enhanced tumourigenic mechanisms, such as cell proliferation, metastasis, invasion, migration and stemness; hence, CD44 is an important clinical target. This review summarises current research regarding the different CD44 isoform structures and their roles and functions in supporting tumourigenesis and discusses CD44 expression regulation, CD44-signalling pathways and interactions involved in cancer development. The clinical significance and prognostic value of CD44 and the potential of CD44 as a therapeutic target in cancer are also addressed.
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