Membrane proteome functional characterization of breast cancer-initiating cells subjected to bone morphogenetic protein signaling inhibition by dorsomorphin

Susy Piovesana*, Anna Laura Capriotti, Valentina Colapicchioni, Francesca Ferraris, Giorgia La Barbera, Salvatore Ventura

*Corresponding author for this work

Abstract

In this study, A17 cells, which are an invasive mesenchymal cell line with cancer stem cell properties, were exploited for the study of the role of bone morphogenetic protein pathways in cancer-initiating cells employing a proteomics-based approach. A17 cells were treated with the bone morphogenetic protein signaling inhibitor dorsomorphin for 3 days. After that, subcellular fractionation of cell samples was performed and the membrane fraction analyzed by shotgun proteomics. The extracted membrane proteins were enzymatically digested and the resulting peptide mixture was analyzed by nano liquid chromatography coupled to tandem mass spectrometry and relative label-free quantitation. Protein profiles of A17 membrane fractions before and after dorsomorphin treatment were compared, and further mined by Gene Ontology search. The protein profile of untreated A17 samples correlated with the mesenchymal phenotype, whereas changes were observed in dorsomorphin-treated samples, further supporting a mesenchymal to epithelial transition upon bone morphogenetic protein signaling pathway inhibition and the importance of this pathway in breast cancer cell malignancy.

Original languageEnglish
JournalMedicinal Chemistry Research
Volume25
Issue number9
Pages (from-to)1971-1979
Number of pages9
ISSN1054-2523
DOIs
Publication statusPublished - 1 Sept 2016

Keywords

  • Bone morphogenetic protein signaling inhibition
  • Breast cancer
  • Dorsomorphin
  • Mass spectrometry
  • Mesenchymal-epithelial transition
  • Proteomics
  • Spectral counting

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