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Metabolism

A TIGAR tale

Nature Reviews Cancer volume 13, pages 522–523 (2013)Cite this article

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Much of the previous work on TIGAR has been carried out in human cells, so Vousden and colleagues first verified that TIGAR functions similarly in mouse cells. Having found no developmental phenotype in Tigar-null mice, the authors then examined whether TIGAR is needed under conditions of tissue stress. Ablation of the intestinal epithelium using ionizing radiation resulted in crypt reformation after 72 hours in wild-type mice. Owing to a transient increase in apoptosis and reduced rates of proliferation, this response was significantly delayed in mice lacking TIGAR. In intestinal sections from TIGAR wild-type mice, immunohistochemisty indicated that the expression of TIGAR is increased after ionizing radiation. TIGAR has previously been shown to reduce the levels of reactive oxygen species (ROS), and in Tigar-knockout mice levels of malondialdehyde (MDA; an indicator of lipid peroxidation and therefore the presence of ROS) were increased after ionizing radiation compared with those in wild-type mice. Similar results were seen in mice treated with cisplatin and in mice given the inflammatory mediator dextran sodium sulphate, which induces colitis and damage to the intestinal epithelium.

TIGAR expression is increased in both primary colon tumours and metastases

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References

  1. Cheung, E. C. et al. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev. Cell 25, 463–477 (2013)

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  1. Nicola McCarthy
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McCarthy, N. A TIGAR tale. Nat Rev Cancer 13, 522–523 (2013). https://doi.org/10.1038/nrc3567

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