Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A- SMase). A- SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A- SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A- SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation.
Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway / L. Bizzozero, D. Cazzato, D. Cervia, E. Assi, F. Simbari, F. Pagni, C. DE PALMA, A. Monno, C. Verdelli, P..R. Querini, V. Russo, E.G.I. Clementi, C. Perrotta. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 21:4(2014 Apr), pp. 507-520.
Titolo: | Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway |
Autori: | BIZZOZERO, LAURA (Primo) PERROTTA, CRISTIANA (Ultimo) (Corresponding) |
Parole Chiave: | animals; cell line, tumor; cell movement; cell proliferation; cyclin-dependent kinase 2; disease progression; down-regulation; female; humans; lung neoplasms; melanoma; melanoma, experimental; mice; mice, inbred C57BL; microphthalmia-associated transcription factor; pigmentation; proto-oncogene proteins c-bcl-2; proto-oncogene proteins c-met; sphingomyelin phosphodiesterase; signal transduction |
Settore Scientifico Disciplinare: | Settore BIO/14 - Farmacologia Settore BIO/13 - Biologia Applicata |
Data di pubblicazione: | apr-2014 |
Rivista: | |
Tipologia: | Article (author) |
Data ahead of print / Data di stampa: | 6-dic-2013 |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/cdd.2013.173 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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