Oncotarget

Research Papers:

Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin

Chien-Lin Chen, Shu-Hui Wang, Po-Chao Chan, Meng-Ru Shen and Hong-Chen Chen _

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Oncotarget. 2016; 7:37260-37276. https://doi.org/10.18632/oncotarget.9403

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Abstract

Chien-Lin Chen1, Shu-Hui Wang1, Po-Chao Chan1, Meng-Ru Shen2,3, Hong-Chen Chen1,4,5

1Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan

2Department of Pharmacology, National Cheng Kung University, Tainan 704, Taiwan

3Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan 704, Taiwan

4Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan

5Rong-Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan

Correspondence to:

Hong-Chen Chen, email: [email protected]

Keywords: PKCδ, E-cadherin, cell junction, phosphorylation

Received: October 15, 2015    Accepted: April 10, 2016    Published: May 17, 2016

ABSTRACT

Proper control of cell-cell adhesion is crucial for embryogenesis and tissue homeostasis. In this study, we show that protein kinase C (PKC)δ, a member of the novel PKC subfamily, localizes at cell-cell contacts of epithelial cells through its C2-like domain in an F-actin-dependent manner. Upon hepatocyte growth factor stimulation, PKCδ is phosphorylated and activated by Src, which then phosphorylates E-cadherin at Thr790. Phosphorylation of E-cadherin at Thr790 diminishes its interaction with β-catenin and impairs the homophilic interaction between the ectodomains of E-cadherin. The suppression of PKCδ by its dominant-negative mutants or specific short-hairpin RNA inhibits the disruption of cell-cell adhesions induced by hepatocyte growth factor. Elevated PKCδ expression in cancer cells is correlated with increased phosphorylation of E-cadherin at Thr790, reduced binding of E-cadherin to β-catenin, and poor homophilic interaction between E-cadherin. Analysis of surgical specimens confirmed that PKCδ is overexpressed in cervical cancer tissues, accompanied by increased phosphorylation of E-cadherin at Thr790. Together, our findings unveil a negative role for PKCδ in cell-cell adhesion through phosphorylation of E-cadherin.


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