The biology and role of CD44 in cancer progression: therapeutic implications.
The biology and role of CD44 in cancer progression: therapeutic implications.
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DOI：
10.1186/s13045-018-0605-5
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发表时间：
2018-05-10
影响因子：
28.5
通讯作者：
Freeman JW
中科院分区：
文献类型：
--
作者：
Chen C;Zhao S;Karnad A;Freeman JW
CD44是一种非激酶跨膜糖蛋白，在包括癌症干细胞在内的几种细胞类型中过度表达，并且经常显示出被认为在癌症发生和进展中起作用的选择性剪接变异体。透明质酸是CD44的主要配体，结合并激活CD44，激活细胞信号通路，诱导细胞增殖，提高细胞存活率，调节细胞骨架变化，增强细胞运动。CD44标准型（CD44s）和特异性CD44变体（CD44v）亚型的不同功能作用尚不完全清楚。CD44v含有额外的肽基序，可以与细胞表面的生长因子和细胞因子相互作用并将其隔离，从而作为辅助受体促进细胞信号传导。此外，CD44v在转移性肿瘤中表达，而CD44v和CD44s之间的转换可能在调节上皮细胞向间质转化（EMT）和癌细胞的适应性可塑性中发挥作用。在这里，我们回顾了CD44的结构和功能特性，CD44在致瘤性中的已知作用，CD44表达的调节以及靶向CD44用于癌症治疗的潜力。
CD44, a non-kinase transmembrane glycoprotein, is overexpressed in several cell types including cancer stem cells and frequently shows alternative spliced variants that are thought to play a role in cancer development and progression. Hyaluronan, the main ligand for CD44, binds to and activates CD44 resulting in activation of cell signaling pathways that induces cell proliferation, increases cell survival, modulates cytoskeletal changes, and enhances cellular motility. The different functional roles of CD44 standard (CD44s) and specific CD44 variant (CD44v) isoforms are not fully understood. CD44v contain additional peptide motifs that can interact with and sequester growth factors and cytokines at the cell surface thereby functioning as coreceptors to facilitate cell signaling. Moreover, CD44v were expressed in metastasized tumors, whereas switching between CD44v and CD44s may play a role in regulating epithelial to mesenchymal transition (EMT) and in the adaptive plasticity of cancer cells. Here, we review current data on the structural and functional properties of CD44, the known roles for CD44 in tumorigencity, the regulation of CD44 expression, and the potential for targeting CD44 for cancer therapy.
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