Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2004;21(6):315-27.
doi: 10.1023/B:GLYC.0000046274.35732.47.

Integration of glycosphingolipid metabolism and cell-fate decisions in cancer and stem cells: review and hypothesis

Erhard Bieberich  1
Affiliations
Review

Integration of glycosphingolipid metabolism and cell-fate decisions in cancer and stem cells: review and hypothesis

Erhard Bieberich. Glycoconj J. 2004.

Abstract

The metabolism of glycosphingolipids is strictly regulated during the mitotic cell cycle. Before the G1-to-S transition, the ceramide and glucosylceramide concentration is elevated. Ceramide induces apoptosis synergistically with the pro-apoptotic protein prostate apoptosis response 4 (PAR-4) that may be asymmetrically inherited during cell division. Only one daughter cell dies shortly after mitosis, a mechanism we suggested to regulate the number of neural stem cells during embryonic development. The progeny cells, however, may protect themselves by converting ceramide to glucosylceramide and other glycosphingolipids. In particular, complex gangliosides have been found to sustain cell survival and differentiation. The cell cycle may thus be a turning point for (glyco)sphingolipid metabolism and explain rapid changes of the sphingolipid composition in cells that undergo mitotic cell-fate decisions. In the proposed model termed "Shiva cycle", progression through the cell cycle, differentiation, or apoptosis may rely on a delicate balance of (glyco)sphingolipid second messengers that modulate the retinoblastoma-dependent G1-to-S transition or caspase-dependent G1-to-apoptosis program. Ceramide-induced cell cycle delay at G0/G1 is either followed by ceramide-induced apoptosis or by conversion of ceramide to glucosylceramide, a proposed key regulatory rheostat that rescues cells from re-entry into a life/death decision at G1-to-S. We propose a mechanistic model for sphingolpid-induced protein scaffolds ("slip") that regulate cell-fate decisions and will discuss the biological consequences and pharmacological potential of manipulating the (glyco)sphingolipid-dependent cell fate program in cancer and stem cells.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Cell Biol. 1997 Oct 6;139(1):205-17 - PubMed
    1. Adv Exp Med Biol. 2001;491:369-402 - PubMed
    1. Int J Oncol. 1999 Mar;14(3):563-70 - PubMed
    1. J Biol Chem. 2001 Aug 31;276(35):32506-14 - PubMed
    1. Cancer Res. 2001 Sep 15;61(18):6892-8 - PubMed

Publication types

Substances

LinkOut - more resources

  NODES
twitter 2