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

. 2023 Aug 17;72(12):2294–2306. doi: 10.1136/gutjnl-2022-329140

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

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

PMC Copyright notice

Model for NOTUM tumour suppressive-to-oncogenic switch during the adenoma-adenocarcinoma transition. In early adenomas resulting from APC inactivation, NOTUM exerts tumour suppressive activity through cleavage of oncogenic glypican 1 from the cell surface. Here, GPC1 acts as an oncogene by potentiating IGF1R activity upstream of mTORC1, and NOTUM antagonises this oncogenic axis (TOP). In contrast, on transition to adenocarcinoma with inactivation of P53 (and on accrual of additional driver mutations), NOTUM functions as an obligate oncogene by inhibiting tumour suppressive TGFßR activity via inactivating cleavage of Glypican 4 from the cell surface, which normally potentiates TGFßR activity upstream of TAK1/Smad signalling.