Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer
Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer
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DOI：
10.1016/j.matbio.2016.10.001
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发表时间：
2017-05-01
期刊：
影响因子：
6.9
通讯作者：
Skandalis, Spyros S.
中科院分区：
文献类型：
--
作者：
Karousou, Evgenia;Misra, Suniti;Skandalis, Spyros S.
透明质酸（HA）的合成、沉积及其与细胞受体CD 44的相互作用是调节肿瘤发生和发展的关键事件。由HA与CD 44相互作用引发的导致致瘤反应的细胞内信号传导途径是复杂的。此外，HA分子可以根据其浓度和大小执行双重功能。CD 44（CD 44 v）的变体亚型的过表达最常与癌症进展相关，而它们的缺失与肿瘤生长的抑制相关。本文综述了肿瘤微环境中透明质酸合成和分泌的调控机制，包括O-GlcNAc化和泛素化、环境因素和microRNA的作用等。此外，我们专注于CD 44与细胞外和细胞内以及细胞膜上的各种蛋白质的作用和相互作用，特别是在癌症干细胞功能中的CD 44-HA轴，以及CD 44/CD 44 v6靶向抑制肿瘤发生的重要性。(C)2016爱思唯尔B. V.保留所有权利。
Synthesis, deposition, and interactions of hyaluronan (HA) with its cellular receptor CD44 are crucial events that regulate the onset and progression of tumors. The intracellular signaling pathways initiated by HA interactions with CD44 leading to tumorigenic responses are complex. Moreover, HA molecules may perform dual functions depending on their concentration and size. Overexpression of variant isoforms of CD44 (CD44v) is most commonly linked to cancer progression, whereas their loss is associated with inhibition of tumor growth. In this review, we highlight that the regulation of HA synthases (HASes) by post-translational modifications, such as O-GIcNAcylation and ubiquitination, environmental factors and the action of microRNAs is important for HA synthesis and secretion in the tumor microenvironment. Moreover, we focus on the roles and interactions of CD44 with various proteins that reside extra- and intracellularly, as well as on cellular membranes with particular reference to the CD44-HA axis in cancer stem cell functions, and the importance of CD44/CD44v6 targeting to inhibit tumorigenesis. (C) 2016 Elsevier B.V. All rights reserved.