癌症进展和治疗靶向中 CD44 激活的状态,The FEBS Journal

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癌症进展和治疗靶向中 CD44 激活的状态
The FEBS Journal ( IF 5.5 ) Pub Date : 2021-09-03 , DOI: 10.1111/febs.16179
Qian Guo ₁ , Cuixia Yang _{1,

2} , Feng Gao _{1,

2}

Affiliation

CD44 是一种非激酶跨膜糖蛋白，在各种类型的细胞中普遍表达，尤其是癌症干细胞 (CSC)，并且与癌症的发作和侵袭性有关。CD44 的主要配体透明质酸 (HA) 与 CD44 结合并相互作用，进而触发下游信号级联反应，从而促进细胞行为，如增殖、运动、侵袭性和化学抗性。CD44-HA 相互作用是细胞特异性的，并且受 CD44 激活状态的强烈影响。因此，HA 与 CD44 的结合对于 CD44 的激活至关重要，在此期间需要阐明详细的调节机制。不同的CD44激活状态分布在人类癌组织和正常组织中；然而，CD44 激活是否是肿瘤发生的关键要求，进展和臭名昭著的 CSC 特性仍有待澄清。对 CD44 激活调控的深入了解可能有助于未来新型靶向药物的开发。在这里，我们回顾了当前关于细胞表面 CD44 激活状态的发现、CD44 激活的潜在调节机制、CD44 激活在肿瘤进展和 CSC 标志中的已知作用，以及 HA 包被的纳米颗粒的潜力靶向激活的 CD44 用于癌症治疗。

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The state of CD44 activation in cancer progression and therapeutic targeting

CD44, a non-kinase transmembrane glycoprotein, is ubiquitously expressed on various types of cells, especially cancer stem cells (CSCs), and has been implicated in cancer onset and aggressiveness. The major ligand for the CD44, hyaluronan (HA), binds to and interacts with CD44, which in turn triggers downstream signaling cascades, thereby promoting cellular behaviors such as proliferation, motility, invasiveness and chemoresistance. The CD44-HA interaction is cell-specific and strongly affected by the state of CD44 activation. Therefore, the binding of HA to CD44 is essential for the activation of CD44 during which the detailed regulatory mechanism needs to be clarified. Different CD44 activation states distribute in human carcinoma and normal tissue; however, whether CD44 activation is a critical requirement for tumor initiation, progression and notorious CSC properties remains to be clarified. A deeper understanding of the regulation of CD44 activation may facilitate the development of novel targeted drugs in the future. Here, we review the current findings concerning the states of CD44 activation on the cell surface, the underlying regulatory mechanisms of CD44 activation, the known role for CD44 activation in tumor progression and CSC hallmarks, as well as the potential of HA-coated nanoparticle for targeting activated CD44 for cancer therapy.

更新日期：2021-09-03

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