Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting

Title: Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting

Volume: 3

Author(s): Olivier Cuvillier, Isabelle Ader, Pierre Bouquerel, Leyre Brizuela, Bernard Malavaud, Catherine Mazerolles and Pascal Rischmann

Affiliation:

Keywords: Antagonists, &, inhibitors, ceramide, sphingolipids, sphingosine, sphingosine kinase-1, sphingosine 1-phosphate, therapeutic antibody

Abstract: Sphingolipid metabolites are critical to the regulation of a number of fundamental biological processes including cancer. Whereas ceramide and sphingosine mediate and trigger apoptosis or cell growth arrest, sphingosine 1- phosphate promotes proliferation, cell survival and angiogenesis. The delicate equilibrium between the intracellular levels of each of these sphingolipids is controlled by the enzymes that either produce or degrade these metabolites. Sphingosine kinase-1 is a crucial regulator of this two-pan balance, because it produces the pro-survival and pro-angiogenic sphingosine 1-phosphate and decreases the amount of both ceramide and sphingosine, the pro-apoptotic sphingolipids. Moreover, its gene is oncogenic, its mRNA is overproduced in several solid tumors, its overexpression protects cells from apoptosis, and its activity is down-regulated by anti-cancer treatments. Therefore, the sphingosine kinase-1/sphingosine 1-phosphate signaling pathway appears to be a target of interest for therapeutic manipulation.

Cite this article as:

Cuvillier Olivier, Ader Isabelle, Bouquerel Pierre, Brizuela Leyre, Malavaud Bernard, Mazerolles Catherine and Rischmann Pascal, Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting, Current Molecular Pharmacology 2010; 3 (2) . https://dx.doi.org/10.2174/1874467211003020053