Skandalis Spyros S
Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.
Cancers (Basel). 2023 Oct 18;15(20):5041. doi: 10.3390/cancers15205041.
CD44 is a single-chain transmembrane receptor that exists in multiple forms due to alternative mRNA splicing and post-translational modifications. CD44 is the main cell surface receptor of hyaluronan as well as other extracellular matrix molecules, cytokines, and growth factors that play important roles in physiological processes (such as hematopoiesis and lymphocyte homing) and the progression of various diseases, the predominant one being cancer. Currently, CD44 is an established cancer stem cell marker in several tumors, implying a central functional role in tumor biology. The present review aims to highlight the contribution of the CD44 short cytoplasmic tail, which is devoid of any enzymatic activity, in the extraordinary functional diversity of the receptor. The interactions of CD44 with cytoskeletal proteins through specific structural motifs within its intracellular domain drives cytoskeleton rearrangements and affects the distribution of organelles and transport of molecules. Moreover, the CD44 intracellular domain specifically interacts with various cytoplasmic effectors regulating cell-trafficking machinery, signal transduction pathways, the transcriptome, and vital cell metabolic pathways. Understanding the cell type- and context-specificity of these interactions may unravel the high complexity of CD44 functions and lead to novel improved therapeutic interventions.
CD44是一种单链跨膜受体，由于mRNA可变剪接和翻译后修饰而存在多种形式。CD44是透明质酸以及其他细胞外基质分子、细胞因子和生长因子的主要细胞表面受体，这些分子在生理过程（如造血和淋巴细胞归巢）以及各种疾病（主要是癌症）的进展中发挥重要作用。目前，CD44是几种肿瘤中已确定的癌症干细胞标志物，这意味着它在肿瘤生物学中具有核心功能作用。本综述旨在强调CD44短细胞质尾巴（缺乏任何酶活性）在该受体非凡功能多样性中的作用。CD44通过其细胞内结构域内的特定结构基序与细胞骨架蛋白相互作用，驱动细胞骨架重排，并影响细胞器的分布和分子运输。此外，CD44细胞内结构域与各种细胞质效应器特异性相互作用，调节细胞运输机制、信号转导途径、转录组和重要的细胞代谢途径。了解这些相互作用的细胞类型和背景特异性可能揭示CD44功能的高度复杂性，并带来新的改进治疗干预措施。
