CD44 glycoprotein in cancer: a molecular conundrum hampering clinical applications.

CD44 glycoprotein in cancer: a molecular conundrum hampering clinical applications.
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DOI:
10.1186/s12014-018-9198-9
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发表时间:
2018
影响因子:
3.8
通讯作者:
Ferreira JA
Ferreira JA
中科院分区:
医学2区
文献类型:
--
作者:
Azevedo R;Gaiteiro C;Peixoto A;Relvas-Santos M;Lima L;Santos LL;Ferreira JA

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CD44是一种高度糖基化的膜受体,在细胞粘附、信号转导和细胞骨架重塑中起关键作用。它也是癌症中研究最多的糖蛋白之一,经常用于干细胞鉴定,并与化疗耐药和转移有关。然而,CD44是一大类剪接变体的统称,它们表现出不同程度的糖基化,并且可能具有不同的功能作用。此外,与歧义命名相关的结构多样性延迟了临床发展。在此,我们试图全面解决这些问题,并系统化CD44命名,为生物标志物的发现设定里程碑。此外,我们支持CD44可能是癌症新抗原的重要来源,很可能是由剪接和/或糖基化改变引起的。发现潜在的靶向CD44(糖)亚型需要糖组学与蛋白质基因组学方法的结合,探索使用基因组学和转录组学生成的定制蛋白质序列数据库。然而,必要的高通量分析和生物信息学工具现在可用于研究CD44在健康和疾病中的作用。
CD44 is a heavily glycosylated membrane receptor playing a key role in cell adhesion, signal transduction and cytoskeleton remodelling. It is also one of the most studied glycoproteins in cancer, frequently explored for stem cell identification, and associated with chemoresistance and metastasis. However, CD44 is a general designation for a large family of splicing variants exhibiting different degrees of glycosylation and, potentially, functionally distinct roles. Moreover, structural diversity associated with ambiguous nomenclature has delayed clinical developments. Herein, we attempt to comprehensively address these aspects and systematize CD44 nomenclature, setting milestones for biomarker discovery. In addition, we support that CD44 may be an important source of cancer neoantigens, most likely resulting from altered splicing and/or glycosylation. The discovery of potentially targetable CD44 (glyco)isoforms will require the combination of glycomics with proteogenomics approaches, exploring customized protein sequence databases generated using genomics and transcriptomics. Nevertheless, the necessary high-throughput analytical and bioinformatics tools are now available to address CD44 role in health and disease.
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