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Src nuclear localization and its prognostic relevance in human osteosarcoma.

Authors
  • Urciuoli, Enrica1, 2
  • Coletta, Ilenia1
  • Rizzuto, Emanuele3
  • De Vito, Rita4
  • Petrini, Stefania5
  • D'Oria, Valentina5
  • Pezzullo, Marco6
  • Milano, Giuseppe Maria7
  • Cozza, Raffaele7
  • Locatelli, Franco7, 8
  • Peruzzi, Barbara1
  • 1 Research Laboratories, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 2 DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy. , (Italy)
  • 3 Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, Rome, Italy. , (Italy)
  • 4 Department of Histopathology, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 5 Confocal Microscopy Core Facility, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 6 Histology Core Facility, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 7 Oncohematology-Clinical Unit, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 8 Department of Pediatrics, University of Pavia, Pavia, Italy. , (Italy)
Type
Published Article
Journal
Journal of Cellular Physiology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2018
Volume
233
Issue
2
Pages
1658–1670
Identifiers
DOI: 10.1002/jcp.26079
PMID: 28671269
Source
Medline
Keywords
License
Unknown

Abstract

Osteosarcoma is the most common malignant bone tumor in children and young adults. The identification of proteins which exhibit different subcellular localization in low- versus high-risk osteosarcoma can be instrumental to obtain prognostic information and to develop innovative therapeutic strategies. Beside the well-characterized membrane and cytoplasmic localization of Src protein, this study evaluated the prognostic relevance of its so-far unknown nuclear compartmentalization. We analyzed the subcellular distribution of total and activated (pY418) Src in a tissue microarray including 60 osteosarcoma samples. Immunohistochemical analyses revealed a variable pattern of Src expression and localization, ranging from negative to high-stained nuclei combined with a substantial cytoplasmic staining for total and activated forms. The analysis of Kaplan-Meier survival curves in relationship to the diverse permutations of cytoplasmic and nuclear staining suggested a correlation between Src subcellular localization and the overall survival (OS) of osteosarcoma patients. In order to explain this different subcellular localization, normal osteoblasts and three osteosarcoma cell lines were used to investigate the molecular mechanism. Once confirmed a variable Src localization also in these cell lines, we demonstrated a correlation between the N-myristoyltransferase enzymes expression and activity and the Src nuclear content. In conclusion, these results described a so-far unknown Src nuclear localization in osteosarcoma cells, suggesting that the combined detection of nuclear and cytoplasmic Src levels can be used as a prognostic marker for osteosarcoma patient survival. A correlation between the N-myristoyltransferase enzymes and the Src subcellular localization was described as well.

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