Titration of ras alters senescent state and influences tumour initiation

HIGHLIGHTS

• What: The authors develop oncogenic RAS dose-escalation models in_vitro and in_vivo, revealing a RAS dose-driven non-linear continuum of downstream phenotypes. The authors propose that the dose -titrating systems can model a non-linear OIS spectrum, including senescence intermediates such as slow-cycling (RPE1 cells) and immune-resistant tumour-initiating states (mouse livers), both characterized by increased progenitor features and a reduced MYC signature. Although the preclinical models are focused on young female mice, a separate long-term cohort in both sexes validated the similar tumorigenic activity of low-RAS expression in male mice (Extended . . .
  

   

  

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