The Role and Function of Sphingolipids in Glioblastoma Multiforme

Abstract

Aberrations in sphingolipid metabolism and thus levels have been implicated in promoting the aggressiveness of glioblastoma multiforme, one of the most lethal cancers in humans. A major player is sphingosine-1-phosphate, that pressures GBM cells to exhibit its hallmarks, leading to increased proliferation, invasiveness, stemness, angiogenesis and death resistance, this indicating a fi ne balance and interplay between S1P function and this malignancy. To the opposite GBM are organized to maintain low their ceramide and sphingomyelin levels, which in turn lead to a loss of growth control and to a gain of death resistance. While the mechanisms of these alterations are emerging, the sphingolipid signaling pathway has been implicated in controlling GBM action and mass, and in mediating the link of malignancy. Here we describe and discuss the current understanding on how GBM cells arm themselves with the abilities of manipulating sphingolipids, especially sphingosine-1-phosphate and ceramide, and how these alterations, through differential interactions, regulate different signaling

Targeting the Sphingolipid Rheostat in Gliomas

“…The two primary metabolites, sphingosine-1-phosphate (S1P) and ceramide, maintain rheostat balance and play opposing roles in cell survival and proliferation [ 11 ]. S1P is a potent promoter of sustained proliferation, while various ceramide species are known for inducing apoptosis [ 11 , 12 ]. The ratio of these two signaling molecules is known as the sphingolipid rheostat ( Figure 1 A), which has profound implications for several cellular processes, including many hallmarks of cancer ( Figure 1 B).…”