Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner [bulk RNA-seq]

Using the adrenal gland as a model, we investigated the interplay between genetic Znrf3 inactivation and the aging microenvironment. We hypothesized that SF1-Cre-driven Znrf3 cKO mice would progress from adrenal hyperplasia to carcinoma with age. Unexpectedly, after an initial phase of hyperplasia, we found that Znrf3 cKO adrenals steadily regress over time. We demonstrate this phenotypic switch from hyperplasia to regression is driven by activation of cellular senescence and a subsequent senescence-associated secretory phenotype (SASP). To identify potential mechanisms that mediate the switch from hyperplasia to regression, we compared transcriptome changes in adrenal glands isolated from Znrf3 cKO mice and littermate controls in females (6-, 9-, and 12-weeks of age) and males (4-, 6-, and 9-weeks of age). Each group contains samples obtained from 4 independent mice.