44 27

Cited 0 times in

WWC1 and NF2 Prevent the Development of Intrahepatic Cholangiocarcinoma by Regulating YAP/TAZ Activity through LATS in Mice

Authors
 Jaeoh Park  ;  Jeong Sik Kim  ;  Ji Hae Nahm  ;  Sang-Kyum Kim  ;  Da-Hye Lee  ;  Dae-Sik Lim 
Citation
 MOLECULES AND CELLS, Vol.43(5) : 491-499, 2020-05 
Journal Title
MOLECULES AND CELLS
ISSN
 1016-8478 
Issue Date
2020-05
MeSH
Adaptor Proteins, Signal Transducing / genetics ; Adaptor Proteins, Signal Transducing / metabolism* ; Animals ; Carcinogenesis / genetics ; Cell Cycle Proteins / genetics ; Cell Cycle Proteins / metabolism* ; Cell Proliferation / genetics ; Cholangiocarcinoma / genetics* ; Cholangiocarcinoma / metabolism ; Cholangiocarcinoma / pathology ; Epithelial Cells / physiology* ; Gene Expression Regulation, Neoplastic ; Intracellular Signaling Peptides and Proteins / genetics* ; Intracellular Signaling Peptides and Proteins / metabolism ; Liver / physiology* ; Mice ; Mice, Transgenic ; Neurofibromin 2 / genetics* ; Neurofibromin 2 / metabolism ; Phosphoproteins / genetics* ; Phosphoproteins / metabolism ; Protein-Serine-Threonine Kinases / genetics ; Protein-Serine-Threonine Kinases / metabolism* ; Tissue Array Analysis ; Transcription Factors / genetics ; Transcription Factors / metabolism*
Keywords
Hippo pathway ; NF2 ; WWC1 ; YAP ; cholangiocarcinoma
Abstract
Hippo signaling acts as a tumor suppressor pathway by inhibiting the proliferation of adult stem cells and progenitor cells in various organs. Liver-specific deletion of Hippo pathway components in mice induces liver cancer development through activation of the transcriptional coactivators, YAP and TAZ, which exhibit nuclear enrichment and are activated in numerous types of cancer. The upstream-most regulators of Warts, the Drosophila ortholog of mammalian LATS1/2, are Kibra, Expanded, and Merlin. However, the roles of the corresponding mammalian orthologs, WWC1, FRMD6 and NF2, in the regulation of LATS1/2 activity and liver tumorigenesis in vivo are not fully understood. Here, we show that deletion of both Wwc1 and Nf2 in the liver accelerates intrahepatic cholangiocarcinoma (iCCA) development through activation of YAP/TAZ. Additionally, biliary epithelial cell-specific deletion of both Lats1 and Lats2 using a Sox9-CreERT2 system resulted in iCCA development through hyperactivation of YAP/TAZ. These findings suggest that WWC1 and NF2 cooperate to promote suppression of cholangiocarcinoma development by inhibiting the oncogenic activity of YAP/TAZ via LATS1/2.
Files in This Item:
T202006767.pdf Download
DOI
10.14348/molcells.2020.0093
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Kyum(김상겸) ORCID logo https://orcid.org/0000-0003-0768-9923
Nahm, Ji Hae(남지해) ORCID logo https://orcid.org/0000-0003-0902-866X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182737
사서에게 알리기
  feedback

qrcode

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

Browse

Links