TY - JOUR
T1 - Membrane proteome functional characterization of breast cancer-initiating cells subjected to bone morphogenetic protein signaling inhibition by dorsomorphin
AU - Piovesana, Susy
AU - Capriotti, Anna Laura
AU - Colapicchioni, Valentina
AU - Ferraris, Francesca
AU - La Barbera, Giorgia
AU - Ventura, Salvatore
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Bone morphogenetic protein signaling inhibition
KW - Breast cancer
KW - Dorsomorphin
KW - Mass spectrometry
KW - Mesenchymal-epithelial transition
KW - Proteomics
KW - Spectral counting
UR - http://www.scopus.com/inward/record.url?scp=84978745441&partnerID=8YFLogxK
U2 - 10.1007/s00044-016-1657-0
DO - 10.1007/s00044-016-1657-0
M3 - Journal article
AN - SCOPUS:84978745441
SN - 1054-2523
VL - 25
SP - 1971
EP - 1979
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 9
ER -