Related Experiment Video

Updated: Jun 11, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
12:27

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors

Published on: June 8, 2022

Runx regulation of sphingolipid metabolism and survival signaling

Anna Kilbey1, Anne Terry, Alma Jenkins

  • 1Molecular Oncology Laboratory, Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom. A.Kilbey@vet.gla.ac.uk

Cancer Research
|July 1, 2010
PubMed

Insights

Runx genes regulate cell fate and cancer. Ectopic Runx expression promotes cancer cell survival by altering sphingolipid metabolism and resisting apoptosis, revealing a link between transcription factors and lipid signaling in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Runx genes (Runx1, 2, and 3) are critical for cell fate during development.
  • In cancer, Runx genes can function as oncogenes or tumor suppressors.
  • Ectopic Runx expression is linked to oncogenic functions, including resistance to apoptosis.

Purpose of the Study:

  • To identify gene targets responsible for the apoptosis-resistant phenotype associated with ectopic Runx expression.
  • To investigate the role of sphingolipid metabolism in Runx-mediated cancer cell survival.

Main Methods:

  • Identified direct transcriptional targets of Runx in sphingolipid metabolism (Sgpp1, Ugcg, St3gal5/Siat9).
  • Utilized mass spectrometry to analyze changes in ceramide and sphingosine 1 phosphate levels.
  • Assessed the impact of Runx expression on apoptosis signaling pathways (c-Jun-NH(2)-kinase and p38(MAPK)).

Main Results:

  • Ectopic Runx directly targets key sphingolipid metabolism enzymes, altering lipid profiles.
  • Runx expression reduced intracellular long-chain ceramides and increased extracellular sphingosine 1 phosphate.
  • Runx opposed c-Jun-NH(2)-kinase and p38(MAPK) activation, suppressing apoptosis induced by TNF-alpha.

Conclusions:

  • Runx transcription factors directly regulate sphingolipid metabolism enzymes.
  • This regulation contributes to cancer cell survival and chemoresistance by modulating lipid signaling.
  • Reveals a novel connection between oncogenic transcription factors and lipid pathways in cancer.

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