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Molecular and nanoscale evaluation of N-cadherin expression in invasive bladder cancer cells under control conditions or GW501516 exposure

Authors
  • Elie-Caille, Céline1
  • Lascombe, Isabelle2
  • Péchery, Adeline2
  • Bittard, Hugues3
  • Fauconnet, Sylvie2, 3
  • 1 FEMTO-ST Institute, Univ. Bourgogne Franche-Comté, CNRS, ENSMM, UTBM, Besançon, France
  • 2 Univ. Bourgogne Franche-Comté, EA3181, LabEx LipSTIC ANR-11-LABX-0021,
  • 3 CHU Besançon,
Type
Published Article
Journal
Molecular and Cellular Biochemistry
Publisher
Springer-Verlag
Publication Date
Jun 09, 2020
Volume
471
Issue
1
Pages
113–127
Identifiers
DOI: 10.1007/s11010-020-03771-1
PMID: 32519230
PMCID: PMC7370938
Source
PubMed Central
Keywords
License
Unknown

Abstract

N-cadherin is a transmembrane glycoprotein expressed by mesenchymal origin cells and is located at the adherens junctions. It regulates also cell motility and contributes to cell signaling. In previous studies, we identified that its anomalous expression in bladder carcinoma was a tumor progression marker. A pharmacological approach to inhibit N-cadherin expression or to block its function could be relevant to prevent disease progression and metastasis development. The morphological exploration of T24 invasive bladder cancer cells by atomic force microscopy (AFM) revealed a spindle-like shape with fibrous structures. By engaging force spectroscopy with AFM tip functionalized with anti-E or anti-N-cadherin antibodies, results showed that T24 cells expressed only N-cadherin as also demonstrated by Western blotting and confocal microscopy. For the first time, we demonstrated by RTqPCR and Western blotting analyses that the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) agonist GW501516 significantly decreased N-cadherin expression in T24 cells. Moreover, high non-cytotoxic doses of GW501516 inhibited confluent T24 cell wound healing closure. By using AFM, a more sensitive nanoanalytical method, we showed that the treatment modified the cellular morphology and diminished N-cadherin cell surface coverage through the decreasing of these adhesion molecule-mediated interaction forces. We observed a greater decrease of N-cadherin upon GW501516 exposure with AFM than that detected with molecular biology techniques. AFM was a complementary tool to biochemical techniques to perform measurements on living cells at the nanometer resolution level. Taken together, our data suggest that GW501516 could be an interesting therapeutic strategy to avoid bladder cancer cell spreading through N-cadherin decrease.

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