Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids.

Published

Journal Article (Review)

The sphingolipids are a family of lipids found ubiquitously in eukaryotic cell membranes. Within the last decade sphingolipids have emerged as active participants in the regulation of cell growth, differentiation, transformation, and cell-cell contact. A prototypic sphingolipid signalling pathway is the 'sphingomyelin cycle,' in which membrane sphingomyelin is hydrolyzed in response to extracellular stimuli, generating the putative second messenger ceramide. Ceramide, in turn, is thought to propagate the signal into the cell interior by the activation of a phosphatase. It is likely that other sphingolipids are components of similar signalling cycles, generating a variety of lipid messengers which participate in as yet undefined pathways. Sphingosine, for example, is a potential breakdown product of all sphingolipids, and is well-known for its pharmacologic inhibition of protein kinase C. However, it is becoming apparent that sphingosine is active in multiple signalling cascades that are independent of protein kinase C, including effects on fibroblast cell growth and the regulation of the retinoblastoma tumor suppressor protein. Similarly, lyso-sphingolipids, while comprising only a minor fraction of the cell's total sphingolipids, are turning out to have biological effects which warrant their investigation as potential signalling molecules. A distinguishing characteristic of sphingolipid breakdown products is their apparent participation in anti-proliferative pathways of cell regulation. Thus, sphingolipid breakdown products can be found to play roles in growth inhibition, induction of differentiation, and programmed cell death. In coordination with other cellular signal transduction pathways, the sphingolipid breakdown products may be the harnesses on cell growth and may also contribute to the suppression of oncogenesis.

Full Text

Duke Authors

Cited Authors

  • Hannun, YA; Linardic, CM

Published Date

  • December 21, 1993

Published In

Volume / Issue

  • 1154 / 3-4

Start / End Page

  • 223 - 236

PubMed ID

  • 8280742

Pubmed Central ID

  • 8280742

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/0304-4157(93)90001-5

Language

  • eng

Conference Location

  • Netherlands