Back to Search
Start Over
Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma
- Source :
- International Journal of Cancer. 131:2537-2546
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
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 epithelial-mesenchymal 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.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
JAG1
Carcinoma, Hepatocellular
Epithelial-Mesenchymal Transition
cell migration
Tumor suppressor gene
Biology
Cell Line, Tumor
medicine
Humans
Vimentin
Serrate-Jagged Proteins
RNA, Messenger
Epithelial–mesenchymal transition
Transcription factor
N-cadherin
Cadherin
Calcium-Binding Proteins
Liver Neoplasms
Twist-Related Protein 1
Runt
Membrane Proteins
Nuclear Proteins
E-cadherin
tumor invasion
jagged-1
Cadherins
digestive system diseases
Gene Expression Regulation, Neoplastic
SNAI2
Core Binding Factor Alpha 3 Subunit
Oncology
embryonic structures
Cancer research
Intercellular Signaling Peptides and Proteins
Immunohistochemistry
Snail Family Transcription Factors
Jagged-1 Protein
Transcription Factors
Subjects
Details
- ISSN :
- 00207136
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- International Journal of Cancer
- Accession number :
- edsair.doi.dedup.....fbb738c51e93264dca4a1f7e0fdcdb2c