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10.1038/cdd.2013.173

http://scihub22266oqcxt.onion/10.1038/cdd.2013.173
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C3950316!3950316!24317198
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suck abstract from ncbi


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pmid24317198      Cell+Death+Differ 2014 ; 21 (4): 507-20
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  • Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway #MMPMID24317198
  • Bizzozero L; Cazzato D; Cervia D; Assi E; Simbari F; Pagni F; De Palma C; Monno A; Verdelli C; Querini PR; Russo V; Clementi E; Perrotta C
  • Cell Death Differ 2014[Apr]; 21 (4): 507-20 PMID24317198show ga
  • 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.
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