2022
DOI: 10.3389/fonc.2022.883831
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CD44 Glycosylation as a Therapeutic Target in Oncology

Abstract: 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 glycosyl… Show more

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Cited by 25 publications
(13 citation statements)
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“…Additionally, high expression of CD44 can promote tumor cell adhesion and migration by interacting with ligands, such as hyaluronic acid, in the extracellular matrix 31 . CD44 is associated with various signaling pathways, including Wnt, Hedgehog, and PI3K/Akt, thereby participating in the regulation of tumor cell proliferation, survival, and transformation processes [32][33][34] . The interactions of CD44 with other cells and molecules in the tumor microenvironment are also important.…”
Section: Discussionmentioning
confidence: 99%
“…Additionally, high expression of CD44 can promote tumor cell adhesion and migration by interacting with ligands, such as hyaluronic acid, in the extracellular matrix 31 . CD44 is associated with various signaling pathways, including Wnt, Hedgehog, and PI3K/Akt, thereby participating in the regulation of tumor cell proliferation, survival, and transformation processes [32][33][34] . The interactions of CD44 with other cells and molecules in the tumor microenvironment are also important.…”
Section: Discussionmentioning
confidence: 99%
“…Due to the central role of growth factors in therapeutic angiogenesis, the association between CD44 and growth factor-induced angiogenic signals has undoubtedly attracted much attention. In addition to the obvious effects of CD44 in regulating the angiogenic phenotype of ECs, some studies demonstrate the positive relationship between the expression of CD44 and proangiogenic growth factors, such as VEGF, FGF2, and so on (Liao et al 2022 ; Ludwig et al 2019 ). Indeed, there have been observations indicating CD44 coordinates with VEGF to promote tumor and ischemia-induced angiogenesis.…”
Section: Discussionmentioning
confidence: 99%
“…Notably, as discussed by Noar et al, in some cases, to bind HA, CD44 needs to be stimulated, activated or deglycosylated [ 36 ]. Indeed, it seems that CD44 N-glycosylation controls the “on” or “off” switch of HA binding to CD44 [ 37 , 38 ].…”
Section: Mechanisms Of Ha Actionmentioning
confidence: 99%