Geometric Confinement Guides the Expression of Cancer Stem Cell Molecular Markers CD44 via Cell Traction Forces

ACS Biomater Sci Eng. 2020 Aug 10;6(8):4623-4630. doi: 10.1021/acsbiomaterials.0c00366. Epub 2020 Jul 30.

Abstract

Cancer stem cells (CSCs) play a critical role in the cancer metastasis and account for tumor heterogeneity. Growing evidence indicates that the CSC phenotypes are related to the tumor microenvironment. In this study, we report that the gradient of mechanical stresses guides the spatial patterning of the expression of CD44 and Yes-associated protein (YAP) in the geometrically confined multicellular sheets. Our study shows that the cytoskeletal contraction regulates the expression of CD44 through the translocation of YAP into the nucleus. The results demonstrate that geometric confinement and mechanical stresses are the regulators in the spatial patterning of CSC. It may help to understand the relationship between the tumor microenvironment and oncogenesis.

Keywords: cancer stem cell; geometric confinement; spatial patterning; traction force.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Humans
  • Hyaluronan Receptors / genetics
  • Neoplasms* / genetics
  • Neoplastic Stem Cells
  • Traction*
  • Tumor Microenvironment

Substances

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