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Matrix Biol. 2017 May;59:3-22. doi: 10.1016/j.matbio.2016.10.001. Epub 2016 Oct 13.

Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer.

Author information

1
Department of Surgical and Morphological Sciences, University of Insubria, 21100, Italy.
2
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
3
Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital F-46, SE-141 86 Stockholm, Sweden.
4
Department of Gynecology and Obstetrics, Münster University Hospital, D-48149 Münster, Germany.
5
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece.
6
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece. Electronic address: skandalis@upatras.gr.

Abstract

Synthesis, deposition, and interactions of hyaluronan (HA) with its cellular receptor CD44 are crucial events that regulate the onset and progression of tumors. The intracellular signaling pathways initiated by HA interactions with CD44 leading to tumorigenic responses are complex. Moreover, HA molecules may perform dual functions depending on their concentration and size. Overexpression of variant isoforms of CD44 (CD44v) is most commonly linked to cancer progression, whereas their loss is associated with inhibition of tumor growth. In this review, we highlight that the regulation of HA synthases (HASes) by post-translational modifications, such as O-GlcNAcylation and ubiquitination, environmental factors and the action of microRNAs is important for HA synthesis and secretion in the tumor microenvironment. Moreover, we focus on the roles and interactions of CD44 with various proteins that reside extra- and intracellularly, as well as on cellular membranes with particular reference to the CD44-HA axis in cancer stem cell functions, and the importance of CD44/CD44v6 targeting to inhibit tumorigenesis.

KEYWORDS:

CD44; Cancer; Cancer stem cells; Hyaluronan; Hyaluronan synthase; Tissue-specific-targeting

PMID:
27746219
DOI:
10.1016/j.matbio.2016.10.001
[Indexed for MEDLINE]

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