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ID 49681
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Author
Tanaka, Shigetomi
Nakanishi, Yutaka
Nishina, Shin-Ichi
Horiguchi, Shigeru
Takaoka, Nobuyuki
Iwamuro, Masaya
Kataoka, Junro
Hagihara, Hiroaki
Toshimori, Junichi
Ohnishi, Hideki
Takaki, Akinobu Kakenhi
Yagi, Takahito Kakenhi
Abstract
Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.
Keywords
cell migration
tumor invasion
jagged-1
E-cadherin
N-cadherin
Published Date
2012-12-01
Publication Title
International Journal of Cancer
Volume
volume131
Issue
issue11
Start Page
2537
End Page
2546
ISSN
0020-7136
NCID
AA00680002
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1002/ijc.27575
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/49134
language
英語
Copyright Holders
© 2012 UICC
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author
Refereed
True
DOI
Web of Sience KeyUT