YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC

Cited 0 time in webofscience Cited 0 time in scopus
46 Viewed 27 Downloaded
Title
YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC
Author(s)
Choi, W; Kim, J; Park, J; Lee, DH; Hwang, D; Kim, JH; Ashktorab, H; Smoot, D; Kim, SY; Choi, C; Gou Young Koh; Lim, DS
Publication Date
2018-06
Journal
CANCER RESEARCH, v.78, no.12, pp.3306 - 3320
Publisher
AMER ASSOC 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. © 2018 American Association for Cancer Research.
URI
https://pr.ibs.re.kr/handle/8788114/4977
ISSN
0008-5472
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
Files in This Item:
3306.full.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse