Nanostructured Architectures Promote the Mesenchymal-Epithelial Transition for Invasive Cells

Zongjie Wang, Fan Xia, Mahmoud Labib, Moloud Ahmadi, Haijie Chen, Jagotamoy Das, Sharif U. Ahmed, Stéphane Angers, Edward H. Sargent, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Dynamic modulation of cellular phenotypes between the epithelial and mesenchymal states - the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) - plays an important role in cancer progression. Nanoscale topography of culture substrates is known to affect the migration and EMT of cancer cells. However, existing platforms heavily rely on simple geometries such as grooved lines or cylindrical post arrays, which may oversimplify the complex interaction between cells and nanotopography in vivo. Here, we use electrodeposition to construct finely controlled surfaces with biomimetic fractal nanostructures as a means of examining the roles of nanotopography during the EMT/MET process. We found that nanostructures in the size range of 100 to 500 nm significantly promote MET for invasive breast and prostate cancer cells. The "METed" cells acquired distinct expression of epithelial and mesenchymal markers, displayed perturbed morphologies, and exhibited diminished migration and invasion, even after the removal of a nanotopographical stimulus. The phosphorylation of GSK-3 was decreased, which further tuned the expression of Snail and modulated the EMT/MET process. Our findings suggest that invasive cancer cells respond to the geometries and dimensions of complex nanostructured architectures.

Original languageEnglish (US)
Pages (from-to)5324-5336
Number of pages13
JournalACS nano
Volume14
Issue number5
DOIs
StatePublished - May 26 2020
Externally publishedYes

Keywords

  • cancer biology
  • electrodeposition
  • epithelial-mesenchymal transition
  • mechanobiology
  • nanostructured microarchitectures

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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