Liao Chengcheng, Wang Qian, An Jiaxing, Chen Jie, Li Xiaolan, Long Qian, Xiao Linlin, Guan Xiaoyan, Liu Jianguo
Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China.
Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, Zunyi, China.
Front Oncol. 2022 Jul 21;12:883831. doi: 10.3389/fonc.2022.883831. eCollection 2022.
The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.
非激酶跨膜糖蛋白CD44与包括透明质酸（HA）在内的配体之间的相互作用与肿瘤的发生和发展密切相关。CD44糖基化的变化可调节其与HA、唾液酸结合免疫球蛋白样凝集素15（Siglec-15）、纤连蛋白、四跨膜蛋白超家族成员5（TM4SF5）、富脯氨酸糖蛋白4（PRG4）、成纤维细胞生长因子2（FGF2）、胶原蛋白和血小板反应蛋白1（podoplanin）的结合，并激活或抑制c-Src/信号转导和转录激活因子3（STAT3）/ Twist1 / B淋巴瘤莫洛尼氏鼠白血病病毒插入位点1（Bmi1）、磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）、细胞外信号调节激酶（ERK）/核因子κB（NF-κB）/ Nanog等信号通路，从而对肿瘤微环境和肿瘤细胞命运产生深远影响。然而，CD44的糖基化很复杂，在很大程度上尚不明确，目前对CD44糖基化如何影响肿瘤的了解有限。在将靶向CD44糖基化应用于治疗人类癌症之前，必须解决这些问题。
