Abstract:
:The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype-ARF suppression-induced senescence (ASIS)-that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Miyawaki S,Kawamura Y,Oiwa Y,Shimizu A,Hachiya T,Bono H,Koya I,Okada Y,Kimura T,Tsuchiya Y,Suzuki S,Onishi N,Kuzumaki N,Matsuzaki Y,Narita M,Ikeda E,Okanoya K,Seino K,Saya H,Okano H,Miura Kdoi
10.1038/ncomms11471subject
Has Abstractpub_date
2016-05-10 00:00:00pages
11471issn
2041-1723pii
ncomms11471journal_volume
7pub_type
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