Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2024 Feb 21;60(5):449–465. doi: 10.1007/s11626-024-00855-w

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Figure 6. — Diverse roles of RNF43 mutations in multistep carcinogenesis. Transient Wnt activation induces wild-type RNF43 in normal cells. RNF43 starts to suppress Wnt signaling via Fzd degradation, but it also suppresses the p53 pathway simultaneously (upper left, diagram). Attenuated Wnt signal reduces RNF43 expression to release p53 suppression, then returns to the resting state. Stem cells can self-renew only in the small window with hi-Wnt and low-p53 state (upper left, graph). Meanwhile, initial Wnt activation in CRCs even weakly induces oncogenic RNF43 and accelerates/amplifies Wnt signaling by forming positive feedback (upper right, diagram). Excess Wnt signal activity and p53 suppression may cause cells to proliferate out of biological control since these oncogenic RNF43 still suppress p53 (upper right, graph). Therefore, the oncogenic mutations of RNF43 in MSI-Hi CRC may simultaneously take the place of two mutations of APC and TP53 of MSS CRC (bottom). mt^Onco, oncomutant.