Long Live The Naked Mole-Rat

A tumor suppressor protein called ARF may be the reason why the naked mole-rat can live up to 30 years and almost never show any type of cancer.

AsianScientist (Jun. 21, 2016) – Naked mole-rats, the longest-living rodent species known to mankind, exhibit extraordinary resistance to cancer. They live up to 30 years and captured colonies almost never show any type of cancer.

A new study into the anti-cancer mechanisms of these animals, published in Nature Communications, may help researchers overcome the challenge of using human induced pluripotent stem cells (iPSCs) for treating patients without introducing the danger of tumor formation.

The collaborative research team, hailing from Hokkaido University and Keio University in Japan, used tissue from adult mole-rats to develop iPSCs, which, like embryonic stem cells, are capable of becoming any type of tissue in the body.

When the mole-rats’ iPSCs were inserted into the testes of mice with extremely weak immune systems, the iPSCs did not form tumors in contrast to human iPSCs and mouse iPSCs. Upon further investigation, they found that a tumor suppressor gene called alternative reading frame (ARF), which is normally suppressed in mouse and human iPSCs, remained active in the mole-rat iPSCs.

The team also found that ERAS, a tumorigenic gene expressed in mouse embryonic stem cells and iPSCs, was mutated and dysfunctional in the mole-rat iPSCs. When the researchers disabled the ARF gene, forced the expression of the mouse ERAS gene in the mole-rat iPSCs, and then inserted them into the mice, the mice grew large tumors.

When they suppressed the ARF gene in mole-rat cells during the reprogramming process to iPSCs, the cells stopped proliferating. The researchers theorized that this ARF suppression-induced senescence (ASIS) further helps protect the naked mole-rat by reducing the chance for tumor formation—a feature that seems to be unique to the naked mole-rat.

“Further research into the detailed mechanisms underlying ASIS in naked mole-rats may shed new light on cancer resistance in the mole-rats and contribute to the generation of non-tumorigenic human-iPSCs, enabling safer cell-based therapeutics,” said Assistant Professor Kyoko Miura from Hokkaido University, the corresponding author of the study.

The article can be found at: Miyawaki et al. (2016) Tumour Resistance in Induced Pluripotent Stem Cells Derived from Naked Mole-Rats.


Source: Hokkaido University; Photo: Mike Fisher/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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