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Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again.
Cell Cycle 2007; 6(5):522-7CC

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.

Authors+Show Affiliations

Children's Hospital Oakland Research Institute, Cancer Center, Oakland, California.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

17361098

Citation

Oskouian, Babak, and Julie Saba. "Sphingosine-1-phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again." Cell Cycle (Georgetown, Tex.), vol. 6, no. 5, 2007, pp. 522-7.
Oskouian B, Saba J. Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again. Cell Cycle. 2007;6(5):522-7.
Oskouian, B., & Saba, J. (2007). Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again. Cell Cycle (Georgetown, Tex.), 6(5), pp. 522-7.
Oskouian B, Saba J. Sphingosine-1-phosphate Metabolism and Intestinal Tumorigenesis: Lipid Signaling Strikes Again. Cell Cycle. 2007 Mar 1;6(5):522-7. PubMed PMID: 17361098.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again. AU - Oskouian,Babak, AU - Saba,Julie, Y1 - 2007/03/21/ PY - 2007/3/16/pubmed PY - 2007/5/4/medline PY - 2007/3/16/entrez SP - 522 EP - 7 JF - Cell cycle (Georgetown, Tex.) JO - Cell Cycle VL - 6 IS - 5 N2 - 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. SN - 1551-4005 UR - https://www.unboundmedicine.com/medline/citation/17361098/Sphingosine_1_phosphate_metabolism_and_intestinal_tumorigenesis:_lipid_signaling_strikes_again_ L2 - http://www.tandfonline.com/doi/full/10.4161/cc.6.5.3903 DB - PRIME DP - Unbound Medicine ER -