The Role and Function of Sphingolipids in Glioblastoma Multiforme

  • Loubna Abdel Hadi
  • Clara Di Vito
  • Giovanni Marfia
  • Stefania Elena Navone
  • Rolando Campanella
  • Laura RiboniEmail author


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 fine 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 pathways, and integrate GBM function and mass, thus providing molecular cues for GBM properties and progression. It is a future challenge unrevealing how the multiforme features of sphingolipid signaling could be effectively manipulated as strategies to optimize the efficacy and selectivity of future therapies for GBM.


Glioblastoma multiforme Glioblastoma hallmarks Sphingolipids Sphingosine-1-phosphate Ceramide Sphingosine kinase Ceramide synthase Sphingomyelinase Glucosylceramide synthase Sphingomyelin synthase 



2-Hydroxyoleic acid


Acid ceramidase


Acid sphingomyelinase


B-cell lymphoma 2-like 13


Basic fibroblast growth factor


CD95 ligand


Ceramide synthase


Extracellular matrix


Epidermal growth factor


Endoplasmic reticulum




Glioblastoma stem-like cells


Hypoxia inducible factor




Neutral sphingomyelinase


Plasminogen activator inhibitor-1


Plasminogen activator system


Protein kinase R-like endoplasmic reticulum kinase


Protein kinase C delta


Phospholipase D


Protein kinase D2


Phosphatase and tensin homolog located on chromosome TEN




Sphingosine-1-phosphate receptors 1–5


Sphingosine-1-phosphate phosphatase 2






Tumor necrosis factor α


Vascular endothelial growth factor


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Loubna Abdel Hadi
    • 1
  • Clara Di Vito
    • 1
  • Giovanni Marfia
    • 2
  • Stefania Elena Navone
    • 2
  • Rolando Campanella
    • 3
  • Laura Riboni
    • 4
    Email author
  1. 1.Department of Medical Biotechnology and Translational Medicine, LITA-SegrateUniversity of MilanMilanItaly
  2. 2.Neurosurgery Unit, Laboratory of Experimental Neurosurgery and Cell Therapy, Fondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly
  3. 3.Neurosurgical UnitSan Carlo Borromeo HospitalMilanItaly
  4. 4.Department of Medical Biotechnology and Translational Medicine, LITA-SegrateUniversity of MilanMilanItaly

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