14-3-3σ represents an intestinal tumor suppressor

Although the 14-3-3σ gene was initially identified as a p53 target gene in colorectal cancer (CRC) cells it remained unknown whether it represents a suppressor of intestinal tumorigenesis. Deletion of 14-3-3σ in ApcMin mouse model of intestinal cancer resulted in an increased number and size of adenomas in the small and large intestine. Consequently, the median survival of these mice was shortened. 14-3-3σ-deficient adenomas displayed an increase in proliferation and decreased apoptosis, as well as increased dysplasia. Global expression profiling of adenomas revealed that loss of 14-3-3σ promoted the acquisition of a mesenchymal-like signature, which was associated with poor, relapse-free survival of CRC patients. In addition, numerous cytokines were up-regulated in 14-3-3σ-deficient adenomas, indicating a role of 14-3-3σ in regulating tumor/stroma interactions. Taken together, these results provide genetic proof of a tumor suppressor function of 14-3-3σ in the intestine. Intestinal adenomas from ApcMin/+ and ApcMin/+/14-3-3σ-/- mice were subjected to RNA-seq analyses. For each genotype, four mice were analyzed.