Use of tumor suppressor genes of naked mole rats for human cancer treatment.

Cancer not only has a significant prevalence in the human population, but is also leading cause of death in animals. Despite a long history, our battle against cancer continues. Cross-species comparative genomics offers insight into shared genes and pathways by analyzing genomic data across species, enhancing our understanding of cancer mechanisms, evolutionary processes, and possible therapeutic targets. However, no previous study has demonstrated the inhibitory effects of tumor suppressor genes from one species on tumor cells from another. The naked mole rat is the only mammal yet to be found with cancer that is attributed to its tumor suppressor genes. In this study, we constructed phylogenetic trees and assessed the anti-tumor activity of two suppressor genes, programmed cell death molecule 5 (PDCD5) and dickkopf 3 (DKK3), from rats, mice, and humans. DKK3 robustly inhibited the proliferation of breast cancer cells within and across species due to its highly conserved protein sequence. However, the cross-species inhibitory effect of PDCD5 on breast cancer cells was inconsistent due to significant sequence variations. Intriguingly, PDCD5 from the naked mole rat demonstrated potent anti-tumor activity against breast cancer cells from mice, rats, and humans, surpassing that of PDCD5 from parental species. Our results demonstrate that the suppressor genes from the naked mole rat have a strong inhibitory effect on cancer cells, indicating that the powerful anti-cancer functions of the naked mole rat may be useful for human tumor treatment.