Insights Into Cancer Resistance From The Blind Mole Rat

The blind mole rat may not be able to see, but its genome could shed light on why it does not develop cancer.

AsianScientist (Jun 5, 2014) – A genomic and transcriptomic study has revealed the genes that allowed the blind mole rat (Spalax galili) to adapt to the stresses of life underground and provides clues as to how it resists cancer. This study has been published in Nature Communications.

The blind mole rat spends its entire life deep underground, which allows it to avoid predators and climatic fluctuations. However, this lifestyle also exposes it to challenges such as low oxygen (hypoxia), high carbon dioxide levels (hypercapnia) and soil pathogens. Oxygen levels as low as 7.2 percent and carbon dioxide as high as 6.1 percent have been recorded in underground burrows, in comparison to typical atmospheric levels of 21 percent and 0.04 percent respectively.

An international team of scientists, led by researchers from BGI, found that the blind mole rat upregulates genes involved in the hypoxia response controlled by the transcription factor HIF-1. Furthermore, a mutation in the p53 gene allows blind mole rat cells to escape hypoxia-induced cell death, thereby avoiding excessive cell loss. The p53 mutation could also have resulted in the observed over-representation of short interspersed elements (SINEs) that is linked not only to hypoxia and hypercapnia tolerance but also the degeneration of vision and resistance to cancer.

The blind mole rat and its closely related cousin, the naked mole rat (Heterocephalus glaber), are famous for their seeming immunity to cancer. Out of thousands of lab-reared animals, none have spontaneously developed cancer; more than that, both mole rats are even resistant to chemical carcinogens.

This cancer resistance could be the result of the adaptation to hypoxia via the weakening of the p53 gene and accompanying SINE expansion. As p53 is also positively involved in the immune response, the authors suggest that the blind mole rat compensated for the loss in immunity via duplication of the Ifnb1 gene, which encodes the pro-inflammatory cytokine interferon beta. Activation of the interferon beta pathway could lead to the death of cells via a recently discovered phenomenon known as TRAIN (for “transcription of repeats activates interferon”), killing them before they have a chance to turn cancerous.

These findings deepen our understanding of adaptations to extreme environments and highlight novel pathways that could be exploited in fighting ageing and cancer.

The article can be found at: Fang et al. (2014) Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax.


Copyright: Asian Scientist Magazine; Photo: Fang et al/Nature Publishing Group.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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