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Hyaluronan-CD44 axis orchestrates cancer stem cell functions.

Spyros S Skandalis1, Theodoros T Karalis1, Athanasios Chatzopoulos1

  • 1Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece.

Cellular Signalling
|July 31, 2019
PubMed
Summary

The CD44-hyaluronan axis is crucial for cancer stem cell (CSC) functions, influencing stemness, drug resistance, and EMT. Targeting this pathway offers potential CSC therapies.

Keywords:
CD44Cancer nicheCancer stem cells (CSCs)Drug resistanceEMTExosomesHyaluronan

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Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • CD44 is a key cancer stem cell (CSC) marker involved in tumor cell signaling.
  • Hyaluronan, CD44's ligand, is abundant in the CSC niche, highlighting the axis's importance.
  • CD44-hyaluronan interactions are critical for CSC phenotype acquisition and maintenance.

Purpose of the Study:

  • To review recent advances on the role of hyaluronan-CD44 interactions in cancer stem cells.
  • To explore the impact of this axis on CSC stemness and drug resistance.
  • To present potential therapeutic strategies targeting the hyaluronan-CD44 axis in CSCs.

Main Methods:

  • Literature review of recent studies on CD44, hyaluronan, and cancer stem cells.
  • Analysis of the functional implications of the hyaluronan-CD44 axis in CSCs.
  • Identification and summary of therapeutic approaches targeting this signaling pathway.

Main Results:

  • The hyaluronan-CD44 axis significantly influences CSC stemness properties.
  • This axis contributes to drug resistance via EMT induction, oxidative stress resistance, and extracellular vesicle secretion.
  • Epigenetic modifications are also modulated by the hyaluronan-CD44 interactions.

Conclusions:

  • The hyaluronan-CD44 axis is a critical regulator of cancer stem cell phenotype and function.
  • Targeting the hyaluronan-CD44 pathway presents a promising therapeutic avenue for overcoming CSC-mediated resistance.
  • Further research into this axis could lead to novel anti-cancer strategies.