Hyaluronan-CD44 axis orchestrates cancer stem cell functions

The prominent role of CD44 in tumor cell signaling together with its establishment as a cancer stem cell (CSC) marker for various tumor entities imply a key role for CD44 in CSC functional properties. Hyaluronan, the main ligand of CD44, is a major constituent of CSC niche and, therefore, the hyalur...

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Bibliographic Details
Published in:Cellular signalling 2019-11, Vol.63, p.109377, Article 109377
Main Authors: Skandalis, Spyros S., Karalis, Theodoros T., Chatzopoulos, Athanasios, Karamanos, Nikos K.
Format: Article
Language:English
Subjects:
Cancer niche
Cancer stem cells (CSCs)
CD44
Drug resistance
EMT
Exosomes
Hyaluronan
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Summary:The prominent role of CD44 in tumor cell signaling together with its establishment as a cancer stem cell (CSC) marker for various tumor entities imply a key role for CD44 in CSC functional properties. Hyaluronan, the main ligand of CD44, is a major constituent of CSC niche and, therefore, the hyaluronan-CD44 signaling axis is of functional importance in this special microenvironment. This review aims to provide recent advances in the importance of hyaluronan-CD44 interactions in the acquisition and maintenance of a CSC phenotype. Hyaluronan-CD44 axis has a substantial impact on stemness properties of CSCs and drug resistance through induction of EMT program, oxidative stress resistance, secretion of extracellular vesicles/exosomes and epigenetic control. Potential therapeutic approaches targeting CSCs based on the hyaluronan-CD44 axis are also presented.
ISSN:0898-6568
1873-3913
1873-3913
DOI:10.1016/j.cellsig.2019.109377