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 suggesteda 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 theN-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.

Src nuclear localization and its prognostic relevance in human osteosarcoma / Urciuoli, Enrica; Coletta, Ilenia; Rizzuto, Emanuele; De Vito, Rita; Petrini, Stefania; D'Oria, Valentina; Pezzullo, Marco; Milano, Giuseppe Maria; Cozza, Raffaele; Locatelli, Franco; Peruzzi, Barbara. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 233:2(2018), pp. 1658-1670. [10.1002/jcp.26079]

Src nuclear localization and its prognostic relevance in human osteosarcoma

Urciuoli, Enrica;COLETTA, ILENIA;Rizzuto, Emanuele;Locatelli, Franco;
2018

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 suggesteda 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 theN-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.
2018
myristoylation; NMTs; osteosarcoma; prognosis; src tyrosine-kinase; acyltransferases; adolescent; adult; biomarkers; tumor; bone neoplasms; cell line; cell nucleus; child; enzyme activation; female; humans; kaplan-meier estimate; male; osteosarcoma; prognosis; protein processing; post-translational; time factors; tissue array analysis; young adult; src-family kinases; physiology; clinical biochemistry; cell biology
01 Pubblicazione su rivista::01a Articolo in rivista
Src nuclear localization and its prognostic relevance in human osteosarcoma / Urciuoli, Enrica; Coletta, Ilenia; Rizzuto, Emanuele; De Vito, Rita; Petrini, Stefania; D'Oria, Valentina; Pezzullo, Marco; Milano, Giuseppe Maria; Cozza, Raffaele; Locatelli, Franco; Peruzzi, Barbara. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 233:2(2018), pp. 1658-1670. [10.1002/jcp.26079]
File allegati a questo prodotto
File Dimensione Formato  
Urciuoli_Src nuclear_2018.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 2.37 MB
Formato Adobe PDF
2.37 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1052874
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact