SAPPORO, Japan, June 16 (UPI) -- Researchers are closer to uncovering the impressive cancer resistance of the naked mole-rat, Heterocephalus glaber, a species that spends most of its life beneath the desert sands of East Africa.
With lifespans of nearly 30 years, naked mole-rats are the planet's longest-living rodents. When captured, colonies of mole-rats rarely exhibit signs of cancer. Recently, scientists in Japan successfully reverted mole-rat skin cells to pluripotent stem cells, an undifferentiated cell with potential to transform into any specific cell type.
Induced pluripotent stem cells, or iPSCs, inserted back into the test subject can develop into tumors called teratomas. When scientists inserted mole-rat iPSCs into the gonads of immune-compromised mice, the mice developed tumors less often than those injected with mice- and human-derived iPSCs.
Researchers found that, unlike iPSCs from mice and humans, mole-rat stem cells continue expressing a tumor suppressor gene called alternative reading frame, or ARF. Another gene called ERAS, which encourages the formation and growth of cancer cells and is found in the embryonic stem cells of mice, was dysfunctional in mole-rat iPSCs.
When scientists turned off ARF gene activation and activated the ERAS gene in mole-rat iPSCs, mice injected with the stem cells grew large tumors.
Researchers from Japan's Hokkaido University shared their results in the journal Nature Communications.
"We conclude that the tumour resistance in NMR-iPSCs is based on NMR-specific ARF regulation and disruption of ERAS," scientists wrote in their paper.
"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," added Kyoko Miura, an assistant professor at Hokkaido.