PMID- 23594797
OWN - NLM
STAT- MEDLINE
DCOM- 20140421
LR  - 20211203
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Linking)
VI  - 11
IP  - 7
DP  - 2013 Jul
TI  - RASSF1A-mediated regulation of AREG via the Hippo pathway in hepatocellular 
      carcinoma.
PG  - 748-58
LID - 10.1158/1541-7786.MCR-12-0665 [doi]
AB  - Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor that is 
      methylated in many human cancers, including hepatocellular carcinoma (HCC). 
      RASSF1A has been shown to suppress tumors via activation of the Hippo tumor 
      suppressor pathway, including mammalian STE20-like kinase (MST). Amphiregulin 
      (AREG), a target gene for Yes-associated protein (YAP), is a known oncogenic 
      component of the Hippo pathway; however, the tumor-suppressive effect of RASSF1A 
      on AREG in regard to regulation of the Hippo pathway remains unclear in HCC. 
      Overexpression of RASSF1A in HCC cells, which lack functional RASSF1A, 
      significantly inhibited cell proliferation and induced apoptosis by activating 
      the Hippo pathway. Consequently, overexpression of RASSF1A inhibited the 
      oncogenic functions of YAP, leading to a significant reduction in AREG secretion 
      via regulation of the Hippo pathway. In human specimens, greater expression of 
      RASSF1A was observed in chronic hepatitis/cirrhosis than in HCC, whereas 
      expression of YAP and AREG was higher in 81% and 86% of HCC than in corresponding 
      chronic hepatitis/cirrhosis, respectively. Furthermore, RASSF1A protein gradually 
      decreased as multistep hepatocarcinogenesis progressed from chronic 
      hepatitis/cirrhosis dysplastic nodules toward HCC, whereas the protein expression 
      of YAP and AREG gradually increased. These findings provide mechanistic insight 
      into the regulation of YAP and AREG by RASSF1A in human multistep 
      hepatocarcinogenesis.
CI  - (c)2013 AACR
FAU - Ahn, Ei Yong
AU  - Ahn EY
AD  - Department of Pathology, Yonsei University College of Medicine, 250 Seongsan-ro, 
      Seodaemun-gu, Seoul, South Korea.
FAU - Kim, Ji Su
AU  - Kim JS
FAU - Kim, Gi Jeong
AU  - Kim GJ
FAU - Park, Young Nyun
AU  - Park YN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130417
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (AREG protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RASSF1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Adult
MH  - Aged
MH  - Amphiregulin
MH  - Apoptosis/genetics
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - DNA Methylation/genetics
MH  - Down-Regulation/genetics
MH  - EGF Family of Proteins
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Glycoproteins/genetics/*metabolism
MH  - Hippo Signaling Pathway
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Liver Neoplasms/genetics/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Phosphoproteins/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - *Signal Transduction/genetics
MH  - Transcription Factors
MH  - Tumor Suppressor Proteins/*metabolism
MH  - Up-Regulation/genetics
MH  - YAP-Signaling Proteins
EDAT- 2013/04/19 06:00
MHDA- 2014/04/22 06:00
CRDT- 2013/04/19 06:00
PHST- 2013/04/19 06:00 [entrez]
PHST- 2013/04/19 06:00 [pubmed]
PHST- 2014/04/22 06:00 [medline]
AID - 1541-7786.MCR-12-0665 [pii]
AID - 10.1158/1541-7786.MCR-12-0665 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2013 Jul;11(7):748-58. doi: 10.1158/1541-7786.MCR-12-0665. Epub 
      2013 Apr 17.