• Oskouian Babak
• Saba Julie

Cell cycle (Georgetown, Tex.)

• Publish Date: Mar 2007
• ISSN: 1551-4005
• Volume: 6
• Issue: 5
• Pages: 522-7
• Medium: Internet
• Language: English
• Citation (JAMA): Oskouian Babak, Saba Julie, et al. Sphingosine-1-phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again.. Cell Cycle Mar 2007;6:522-7

Abstract

Sphingolipids are an evolutionary conserved class of membrane lipids synthesized by all eukaryotic cells. The biological functions of sphingolipids are diverse, encompassing structural roles through their participation in membrane lipid rafts, and informational roles via the involvement of their metabolites in signal transduction pathways. An important sphingolipid metabolite is sphingosine-1-phosphate (S1P), which acts through G protein-coupled receptors present on mammalian cells, thereby stimulating cell proliferation, angiogenesis and inhibiting apoptosis. The main enzyme responsible for S1P synthesis, sphingosine kinase 1 (Sphk1), behaves as an oncogene in experimental systems and is required for polyp enlargement in the Min mouse model of intestinal tumorigenesis. S1P is irreversibly degraded by S1P lyase (SPL), an enzyme that is highly expressed in enterocytes, where it is involved in metabolism of dietary sphingolipids. Forced expression of SPL sensitizes human cells to various stressful stimuli and enhances apoptotic cell death. SPL expression is induced in response to DNA damaging agents in a time- and concentration-dependent manner. On the other hand, SPL is downregulated in human colon cancers and in Min mouse adenomas compared to adjacent uninvolved tissues. These observations suggest that SPL, like Sphk1, may play a role in tumorigenesis. Added support for this notion comes from the fact that S1P-specific antibodies slow tumor progression and angiogenesis in murine xenograft and allograft models. Together, these recent studies have established a link between S1P signaling, metabolism and carcinogenesis that may have implications regarding colon cancer screening, dietary chemoprevention and therapeutics.

This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.

Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.

The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.