YAP targetome reveals activation of SPEM in gastric pre-neoplastic progression and regeneration

Autor: Adrian K.H. Loe, Abilasha Rao-Bhatia, Zhao Wei, Jung-Eun Kim, Bingxin Guan, Yan Qin, Minji Hong, Hyo Sang Kwak, Xiaoyu Liu, Leyi Zhang, Jeffrey L. Wrana, Haiyang Guo, Tae-Hee Kim
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 12, Pp 113497- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.113497
Popis: Summary: 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.
Databáze: Directory of Open Access Journals