YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC

Cited 4 time in webofscience Cited 0 time in scopus
  • Hit : 146
  • Download : 26
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. (C) 2018 AACR.
Publisher
AMER ASSOC CANCER RESEARCH
Issue Date
2018-06
Language
English
Article Type
Article
Citation

CANCER RESEARCH, v.78, no.12, pp.3306 - 3320

ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-17-3487
URI
http://hdl.handle.net/10203/244308
Appears in Collection
MSE-Journal Papers(저널논문)BS-Journal Papers(저널논문)
Files in This Item
105202.pdf(2.74 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 4 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0