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Title 

YAP/TAZ initiates gastric tumorigenesis via upregulation of MYC

Authors 

W ChoiJ KimJ ParkD H LeeD HwangJ H KimH AshktorabD SmootSeon-Young KimC ChoiG Y KohD S Lim

Publisher 

American Association for Cancer Research

Issue Date 

2018

Citation 

Cancer Research

Abstract 

YAP and TAZ play oncogenic roles in various organs, but the role of YAP/TAZ in gastric cancer remains unclear. Here, we show that YAP/TAZ activation initiates gastric tumorigenesis in vivo and verify its significance in human gastric cancer. In mice, YAP/TAZ activation in the pyloric stem cell led to stepwise tumorigenesis. RNA sequencing identified MYC as a decisive target of YAP, which controls MYC at transcriptional and posttranscriptional levels. These mechanisms tightly regulated MYC in homeostatic conditions, but YAP activation altered this balance by impeding miRNA processing, causing a shift towards MYC upregulation. Pharmacologic inhibition of MYC suppressed YAP-dependent phenotypes in vitro and in vivo, verifying its functional role as a key mediator. Human gastric cancer samples also displayed a significant correlation between YAP and MYC. We reanalyzed human transcriptome data to verify enrichment of YAP signatures in a subpopulation of gastric cancers and found that our model closely reflected the molecular pattern of patients with high YAP activity. Overall, these results provide genetic evidence of YAP/TAZ as oncogenic initiators and drivers for gastric tumors with MYC as the key downstream mediator. These findings are also evident in human gastric cancer, emphasizing the significance of YAP/TAZ signaling in gastric carcinogenesis. Significance: YAP/TAZ activation initiates gastric carcinogenesis with MYC as the key downstream mediator

ISSN 

0008-5472

Link 

http://dx.doi.org/10.1158/0008-5472.CAN-17-3487

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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