The same mutations on the TRAMP background, as a secondary oncogenic insult, exacerbated the stress responses through PERK‐ and IRE1‐mediated UPR and pathways, promoting cell growth and differentiation (including ERK1/2 and RAS signalling, Fig 6C and D) that initiated and promoted prostate cancer in the mutant strains compared with the WT‐TRAMP mice. This evidence concerns the gene ERN1 and prostate carcinoma.