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. Here, ERN1 is linked to prostate cancer.