Reply to: Transformation of naked mole-rat cells

It has been independently demonstrated by us and Liang et al. that naked mole-rat (NMR) cells are more resistant to SV40LT and H-RasV12-induced transformation than mouse cells. In the accompanying comment, Hadi et al. argued that NMR cells and mouse cells are equally susceptible to oncogenic transformation by SV40LT and H-RasV12. However, their observations are based on much higher expression levels of H-RasV12 than in our study and Liang et al.’s study. Our new RNA-seq data shows that NMR cells are strikingly more resistant to transcriptomic changes induced by oncogenic Ras than mouse, blind mole-rat, and human cells, revealing suppressed Ras signaling as an anti-cancer mechanism in NMR cells. Furthermore, we found that high expression of H-RasV12 abolished this mechanism and rendered NMR cells susceptible to oncogenic transformation. Our results explain that the ostensibly equal susceptibility of NMR and mouse cells to transformation observed by Hadi et al. was resulted from high levels of H-RasV12 overriding anti-cancer mechanisms of the naked mole rat.