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YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC
  • 작성일2019-05-14
  • 최종수정일2019-05-27
  • 담당부서연구기획과
  • 연락처043-719-8033
  • 972
Cancer Research, 2018, 78(12), 3306─3320, DOI: https://doi.org/10.1158/0008-5472.CAN-17-3487

YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC

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

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 tranional and posttranional 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 tranome 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.



  • 본 연구는 질병관리본부 연구개발과제(과제번호 2018-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
  • This research was supported by a fund(code 2018-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.


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