A, The KPwm/+C mouse model incorporates a mutant p53 allele that converts from constitutive wildtype p53 to mutant p53R172H expression after cre-mediated recombination. Mutant p53R172H is somatically expressed in pancreatic epithelial cells and wildtype p53 is expressed in stromal cells present in the TME. B, The KPfl/+C mouse model incorporates a loss-of-function p53 allele with loxP sites flanking exons 2–11. Wildtype p53 is somatically deleted in pancreatic epithelial cells following cre-recombination and wildtype p53 is expressed in stromal cells present in the TME. C, Mutant p53 is expressed and stabilized in pancreatic tumor cells in KPwm/+C mice. Wildtype p53 expression is lost in pancreatic tumor cells in KPfl/+C mice. Scale bar, 250μM. D, Representative histology of a liver metastasis in a KPwm/+C mouse. Scale bar, 250μM. E, The incidence of liver or lung metastasis in KPwm/+C and KPfl/+C PDAC models. P value determined by unpaired two-tailed t-test. F, Single tumor cells from KPwm/+C and KPfl/+C mice were positively selected by FACS based on a tdTomato reporter. G, Volcano plot of genes differentially expressed in enriched PDAC cell populations in KPwm/+C (n=4) versus KPfl/+C (n=4) mice. H, Enrichr-KEGG analysis of KPwm/+C tumors demonstrates enriched transcriptional misregulation in cancer.