Missense Mutant p53 Transactivates Wnt/β-Catenin Signaling in Neighboring p53-Destabilized Cells through the COX-2/PGE2 Pathway.

ABSTRACT:

Abstract

Missense-type p53 mutations have shown to acquire novel oncogenic roles through a gain-of-function mechanism. However, there is intratumor heterogeneity in stabilization of mutant p53 protein, and it has not been well understood about the interaction between p53-stabilized and -destabilized cells in the same tumors. We established mouse intestinal tumor–derived organoids carrying ApcΔ716, KrasG12D, and Tgfbr2−/− mutations with Trp53R270H or Trp53Null mutation (AKTPR270H and AKTPNull, respectively). Using these organoids, we found that the activation level of Wnt/β-catenin signaling is significantly higher in AKTPR270H cells compared with AKTPNull cells. Notably, Wnt activation in the AKTPNull cells was significantly increased when co-cultured with AKTPR270H cells. Expressi

SUBMITTER: Nakayama M 

PROVIDER: S-EPMC11695814 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature