KLF4-Mediated CDH3 Upregulation Suppresses Human Hepatoma Cell Growth and Migration via GSK-3β Signaling.

Abstract	P-cadherin (CDH3), a classical cell adhesion molecule involved in tissue integrity and cell localization, has been implicated in many types of cancer. However, little is known about its function and regulatory mechanism in hepatocellular carcinoma (HCC). Here we report that CDH3 was positively regulated by kr¨uppel-like transcription factor 4 (KLF4), which is a crucial tumor suppressor gene in HCC, at mRNA level in HCC cell lines. Luciferase reporter assay and chromatin immunoprecipitation assay indicated that KLF4 directly bound to CDH3 promoter and transcriptionally activated CDH3 expression. Consistently, CDH3 expression was closely related with KLF4 expression in patients' samples and both proteins exhibited a downregulated expression pattern in cancer samples. Functionally, enforced CDH3 expression suppressed and silenced CDH3 expression promoted HCC cell growth and migration in vitro. Mechanistically, we observed that GSK-3β was regulated by CDH3 and may function as a possible downstream effector of CDH3. Knockdown of GSK-3β showed a similar phenotype with CDH3 silencing. Taken together, these findings establish the KLF4/CDH3/GSK-3β axis as an important regulatory mechanism in HCC development.
Authors	Li Li, Shijun Yu, Qiong Wu, Ning Dou, Yandong Li, Yong Gao
Journal	International journal of biological sciences (Int J Biol Sci) Vol. 15 Issue 5 Pg. 953-961 ( 2019) ISSN: 1449-2288 [Electronic] Australia
PMID	31182916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CDH3 protein, human Cadherins KLF4 protein, human Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Glycogen Synthase Kinase 3 beta
Topics	Blotting, Western Cadherins (metabolism) Carcinoma, Hepatocellular (metabolism) Cell Movement (physiology) Cell Proliferation (physiology) Gene Expression Regulation, Neoplastic Glycogen Synthase Kinase 3 beta (metabolism) Humans Immunohistochemistry Kruppel-Like Factor 4 Kruppel-Like Transcription Factors (metabolism) Liver Neoplasms (metabolism) Signal Transduction Tissue Array Analysis

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