Expression of sphingosine kinase-1 (SphK-1) correlates with poor survival of tumor patients. This effect is probably due to the capability of SphK-1 to be released into the extracellular medium where it catalyzes the biosynthesis of sphingosine 1-phosphate (S1P), a signalling molecule endowed with profound proangiogenic effects. SphK-1 is a leader-less protein and it is secreted by unconventional mechanism. We report that in human hepatocarcinoma Sk-Hep1 cells, targeting of the enzyme to the cell surface is induced by extracellular signalling and parallels targeting of FGF-2 to the budding vesicles. We also show that SphK-1 is present in a catalitycally active form in vesicles shed by SK-Hep1 and human breast carcinoma 8701-BC cells. The enzyme substrate sphingosine is present in shed vesicles where it is produced by neutral ceramidase. Shed vesicles are therefore a site for S1P production in the extracellular medium, and conceivably also within host cell, after vesicle endocytosis.
|Numero di pagine||10|
|Rivista||Journal of Oncology|
|Stato di pubblicazione||Published - 2010|
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