Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece.
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece.
Cell Signal. 2019 Nov;63:109377. doi: 10.1016/j.cellsig.2019.109377. Epub 2019 Jul 27.
The prominent role of CD44 in tumor cell signaling together with its establishment as a cancer stem cell (CSC) marker for various tumor entities imply a key role for CD44 in CSC functional properties. Hyaluronan, the main ligand of CD44, is a major constituent of CSC niche and, therefore, the hyaluronan-CD44 signaling axis is of functional importance in this special microenvironment. This review aims to provide recent advances in the importance of hyaluronan-CD44 interactions in the acquisition and maintenance of a CSC phenotype. Hyaluronan-CD44 axis has a substantial impact on stemness properties of CSCs and drug resistance through induction of EMT program, oxidative stress resistance, secretion of extracellular vesicles/exosomes and epigenetic control. Potential therapeutic approaches targeting CSCs based on the hyaluronan-CD44 axis are also presented.
CD44 在肿瘤细胞信号中的突出作用及其作为各种肿瘤实体的癌症干细胞 (CSC) 标志物的确立，意味着 CD44 在 CSC 功能特性中起着关键作用。透明质酸是 CD44 的主要配体，是 CSC 生态位的主要组成部分，因此透明质酸-CD44 信号轴在这个特殊的微环境中具有重要的功能意义。本综述旨在提供透明质酸-CD44 相互作用在获得和维持 CSC 表型中的重要性的最新进展。透明质酸-CD44 轴通过诱导 EMT 程序、氧化应激抗性、细胞外囊泡/外泌体的分泌和表观遗传控制，对 CSCs 的干性特性和耐药性产生重大影响。还提出了基于透明质酸-CD44 轴的针对 CSCs 的潜在治疗方法。
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