YAP targetome reveals activation of SPEM in gastric pre-neoplastic progression and regeneration.
Cell Rep
; 42(12): 113497, 2023 12 26.
Article
de En
| MEDLINE
| ID: mdl-38041813
ABSTRACT
Peptic ulcer disease caused by environmental factors increases the risk of developing gastric cancer (GC), one of the most common and deadly cancers in the world. However, the mechanisms underlying this association remain unclear. A major type of GC uniquely undergoes spasmolytic polypeptide-expressing metaplasia (SPEM) followed by intestinal metaplasia. Notably, intestinal-type GC patients with high levels of YAP signaling exhibit a lower survival rate and poor prognosis. YAP overexpression in gastric cells induces atrophy, metaplasia, and hyperproliferation, while its deletion in a Notch-activated gastric adenoma model suppresses them. By defining the YAP targetome genome-wide, we demonstrate that YAP binds to active chromatin elements of SPEM-related genes, which correlates with the activation of their expression in both metaplasia and ulcers. Single-cell analysis combined with our YAP signature reveals that YAP signaling is activated during SPEM, demonstrating YAP as a central regulator of SPEM in gastric neoplasia and regeneration.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Peptides
/
Tumeurs de l'estomac
Limites:
Humans
Langue:
En
Journal:
Cell Rep
Année:
2023
Type de document:
Article
Pays d'affiliation:
Canada