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2016 Fiscal Year Final Research Report

Molecular switch for WNT5A/B expression through TCF-4 isoforms in human liver cancer cells

Research Project

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Project/Area Number 26461025
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKurume University

Principal Investigator

Koga Hironori  久留米大学, 医学部, 教授 (90268855)

Project Period (FY) 2014-04-01 – 2017-03-31
KeywordsWntシグナル / T-cell factor-4 / 癌幹細胞
Outline of Final Research Achievements

We have demonstrated that a mutant isoform (269A) of the SxxSS-harboring TCF-4K robustly expressed WNT5A at both mRNA and protein levels in human liver cancer cells. ChIP assay revealed that the mutant TCF-4 could directly bind to promoter region of WNT5A gene, suggesting the motif contributed to regulate the gene expression. Knockdown of WNT5A resulted in upregulation of the EMT regulator SLUG. These findings suggest that TCF-4 regulates WNT5A expression in a SxxSS motif-dependent manner, thereby contributing to phenotypic changes, including EMT. I addition, HIPK-2 was suggested to be responsible for phosphorylation of serine residues of SxxSS.

Free Research Field

消化器病学

URL: 

Published: 2018-03-22  

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