American Association for Cancer Research
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Figure S5 from YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC

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journal contribution
posted on 2023-03-31, 02:08 authored by Wonyoung Choi, Jeongsik Kim, Jaeoh Park, Da-Hye Lee, Daehee Hwang, Jeong-Hwan Kim, Hassan Ashktorab, Duane Smoot, Seon-Young Kim, Chan Choi, Gou Young Koh, Dae-Sik Lim

MYC is post-transcriptionally upregulated by YAP


National Creative Research Initiatives Center Program

Korean Foundation for Cancer Research

Institute for Basic Science funded by the Ministry of Science



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 step-wise 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. Cancer Res; 78(12); 3306–20. ©2018 AACR.