Hyaluronan-CD44 axis orchestrates cancer stem cell functions

Cell Signal. 2019 Nov:63:109377. doi: 10.1016/j.cellsig.2019.109377. Epub 2019 Jul 27.

Abstract

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.

Keywords: CD44; Cancer niche; Cancer stem cells (CSCs); Drug resistance; EMT; Exosomes; Hyaluronan.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / physiology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Drug Resistance, Neoplasm / physiology*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Hyaluronan Receptors / physiology*
  • Hyaluronic Acid / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Hyaluronic Acid