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Proteomics of dedifferentiation of SK-N-BE2 neuroblastoma cells

Artikel i vetenskaplig tidskrift
Författare Ravi Kanth Rao Saini
S. Attarha
C. D. Santos
J. Kolakowska
Keiko Funa
S. Souchelnytskyi
Publicerad i Biochemical and Biophysical Research Communications
Volym 454
Nummer/häfte 1
Sidor 202-209
ISSN 0006-291X
Publiceringsår 2014
Publicerad vid Sahlgrenska Cancer Center
Sidor 202-209
Språk en
Länkar dx.doi.org/10.1016/j.bbrc.2014.10.0...
Ämnesord Neuroblastoma, Dedifferentiation, Proteomics, DISC1, DNA-PKcs, STEM-CELLS, IDENTIFICATION, BIOLOGY, Biochemistry & Molecular Biology, Biophysics
Ämneskategorier Biokemi och molekylärbiologi, Biofysik

Sammanfattning

Neuroblastoma develops through processes which include cellular dedifferentiation. Ability of tumors to form spheroids is one of the manifestations of dedifferentiation and carcinogenic transformation. To study mechanisms of dedifferentiation of neuroblastoma cells, we generated spheroids and performed a proteomics study to compare the spheroids with parental SK-N-BE2 cells. We observed that dedifferentiation induced extensive changes in the proteome profiles of the cells, which affected more than 30% of detected cellular proteins. Using mass spectrometry, we identified 239 proteins affected by dedifferentiation into spheroids as compared to the parental cells. These proteins represented such regulatory processes as transcription, cell cycle regulation, apoptosis, cell adhesion, metabolism, intracellular transport, stress response, and angiogenesis. A number of potent regulators of stemness, differentiation and cancer were detected as subnetworks formed by the identified proteins. Our validation tissue microarray study of 30 neuroblastoma cases confirmed that two of the identified proteins, DISC1 and DNA-PKcs, had their expression increased in advanced malignancies. Thus, our report unveiled extensive changes of the cellular proteome upon dedifferentiation of neuroblastoma cells, indicated top subnetworks and clusters of molecular mechanisms involved in dedifferentiation, and provided candidate biomarkers for clinical studies. (C) 2014 Elsevier Inc. All rights reserved.

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