Regulation of death and growth signals at the plasma membrane by sphingomyelin synthesis: Implications for hematological malignancies

Elodie Lafont, Kazuyuki Kitatani, Toshiro Okazaki, Bruno Ségui

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Resistance to death receptor ligands (such as FasL and TRAIL) and anticancer treatments is a hallmark of cancer cells. Ceramide, a biologically active sphingolipid, antagonizes cell growth and promotes apoptosis and non-apoptotic forms of cell death. The intracellular levels of ceramide are highly regulated via complex metabolic pathways. Sphingomyelin synthases (SMS) 1 and 2 convert ceramide to sphingomyelin (SM), a ubiquitous phospholipid in mammals. A growing body of evidence in the literature indicates that SMSs likely modulate hematological cell growth and sensitivity to stress-induced apoptosis. On one hand, complete and sustained inhibition of SMS activity is likely to alter membrane composition and properties through membrane SM depletion, perturbing intracellular signaling pathways and leukemia cell growth and conferring partial resistance to death receptor ligands. On the other hand, different patents & reports point to anti-apoptotic functions for SMSs. In patients with chemoresistant leukemia, a decreased intracellular ceramide level was associated with a higher SMS activity. Thus, SMSs and cofactors may constitute original pharmacological targets to treat leukemia.

Original languageEnglish
Pages (from-to)324-333
Number of pages10
JournalRecent Patents on Anti-Cancer Drug Discovery
Volume6
Issue number3
DOIs
Publication statusPublished - 2011 Sep

Keywords

  • Cancer
  • Cell death
  • Cell proliferation
  • Ceramide
  • Sphingolipids
  • Sphingomyelin synthase

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Cancer Research
  • Pharmacology (medical)

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