Fig. 3

Surviving hypoxia: TP53 mutant selection and evolvability

Figure illustrates multiple fitness impacts in cells surviving hypoxic intra-tumour environments via TP53 LOF. These phenotypic features compound to increase adaptive evolvability enabling both metastasis and drug resistance. EMT, epithelial-mesenchymal transition. The curved line is to indicate that EMT is a response to hypoxia (see text for explanation), but is only likely to happen if cells can survive hypoxia/acidosis-associated cell death. Which in turn is much more probable if TP53 signalling is aborted. Note that ocogenic or genotoxic stress can also select for TP53 LOF in the absence of hypoxia and with the same fitness benefits. However, the overall impact on evolvability will be less in the absence of hypoxia-driven EMT