DNA demethylation of claudin-4 suppresses migration and invasion in laryngeal squamous carcinoma cells

Yafang Liu; Kai Chang; Kexin Fu; Xinjie Dong; Xiaoshuai Chen; Jixuan Liu; Ni Cui; Jinsong Ni

doi:10.1016/j.humpath.2018.02.005

DNA demethylation of claudin-4 suppresses migration and invasion in laryngeal squamous carcinoma cells

Hum Pathol. 2018 May:75:71-80. doi: 10.1016/j.humpath.2018.02.005. Epub 2018 Feb 13.

Authors

Yafang Liu¹, Kai Chang², Kexin Fu³, Xinjie Dong⁴, Xiaoshuai Chen⁵, Jixuan Liu⁶, Ni Cui⁷, Jinsong Ni⁸

Affiliations

¹ Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: 41869653@qq.com.
² Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China; Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610000, China. Electronic address: cknyn@foxmail.com.
³ Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: fukexin19910227@126.com.
⁴ Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: dongdong1823@126.com.
⁵ Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: 476207312@qq.com.
⁶ Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: 153909833@qq.com.
⁷ Department of Gastrointestinal Colorectal and Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, China. Electronic address: 312063516@qq.com.
⁸ Department of Pathology, the First Bethune Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: nijs@jlu.edu.cn.

PMID: 29447921
DOI: 10.1016/j.humpath.2018.02.005

Abstract

Claudin-4 (CLDN4) is a member of the claudin transmembrane protein family, which consists of integral membrane proteins that are components of the epithelial cell tight junctions; these tight junctions regulate movement of solutes and ions through the paracellular space. CLDN4 is also a differentiation marker and is believed to indicate an epithelial phenotype. However, the role of CLDN4 in laryngeal squamous carcinoma is still unclear. Here, we showed that CLDN4 expression was down-regulated in laryngeal squamous carcinoma tissues and negatively correlated with methyl-CpG-binding protein 2. In addition, CLDN4 was hypermethylated in HEp-2 cells. DNA demethylation of CLDN4 by 5-aza-2'-deoxycytidine suppressed migration and invasion of HEp-2 cells, whereas CLDN4 silencing restored the migration and invasion of HEp-2 cells. Therefore, CLDN4 plays a key role in laryngeal squamous carcinoma progression.

Keywords: CLDN4; Invasion; Laryngeal squamous carcinoma; Methylation; Migration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Cell Line, Tumor
Cell Movement / physiology
Claudin-4 / biosynthesis*
DNA Demethylation*
Female
Gene Expression Regulation, Neoplastic / physiology
Humans
Laryngeal Neoplasms / metabolism
Laryngeal Neoplasms / pathology*
Male
Middle Aged
Neoplasm Invasiveness / pathology
Squamous Cell Carcinoma of Head and Neck / metabolism
Squamous Cell Carcinoma of Head and Neck / pathology*

Substances

CLDN4 protein, human
Claudin-4