CD44S-hyaluronan interactions protect cells resulting from EMT against anoikis

Matrix Biol. 2015 Oct:48:55-65. doi: 10.1016/j.matbio.2015.04.010. Epub 2015 Apr 30.

Abstract

The detachment of normal epithelial cells from matrix triggers an apoptotic response known as anoikis, during homeostatic turnover. Metastatic tumor cells evade anoikis, by mechanisms that are only partly characterized. In particular, the epithelial-mesenchymal transition (EMT) in a subset of invasive tumor cells confers anoikis-resistance. In some cases, EMT up-regulates the cancer stem cell marker CD44S and the enzyme hyaluronic acid synthase-2 (HAS2). CD44S is the major receptor for hyaluronan in the extracellular matrix. Herein, we demonstrate that CD44S, unlike the CD44E isoform expressed in normal epithelial cells, contributes to the protection against anoikis. This protection requires the interaction of CD44S with hyaluronan (HA). CD44S-HA interaction is proposed to play an important role in tumor metastasis through enhanced cell survival under detached conditions.

Keywords: Anoikis; Apoptosis; CD44; Epithelial-mesenchymal transition; Hyaluronan.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anoikis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition*
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Hyaluronan Synthases
  • Hyaluronic Acid / metabolism*
  • Protein Binding
  • Signal Transduction

Substances

  • CD44S antigen
  • Hyaluronan Receptors
  • Hyaluronic Acid
  • Glucuronosyltransferase
  • HAS2 protein, human
  • Hyaluronan Synthases