Chloride intracellular channel 1 as a switch among tumor behaviors in human esophageal squamous cell carcinoma.

Tomohiro Arita,Shuhei Komatsu,Toshiyuki Kobayashi,Atsushi Shiozaki,Kazuma Okamoto,Yoshito Nako,Katsutoshi Shoda,Toshiyuki Kosuga,Hitoshi Fujiwara,Yoshinori Marunaka,Eigo Otsuji,Mitsuo Kishimoto,Eiichi Konishi,Takeshi Kubota,Hirotaka Konishi,Daisuke Ichikawa

doi:10.18632/oncotarget.25296

Tomohiro Arita, Shuhei Komatsu + Show 14 more

Open Access

https://doi.org/10.18632/oncotarget.25296

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Abstract

Background: Recent studies have reported important roles for chloride intracellular channel 1 (CLIC1) in various cancers; however, its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of the present study was to investigate the role of CLIC1 in human ESCC. Methods: CLIC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted with CLIC1 siRNA, and their effects on cell proliferation, the cell cycle, apoptosis, migration, and invasion were analyzed. The gene expression profiles of cells were analyzed using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. Results: ESCC cells strongly expressed CLIC1. The depletion of CLIC1 using siRNA inhibited cell proliferation, induced apoptosis, and promoted cell migration and invasion. The results of the microarray analysis revealed that the depletion of CLIC1 regulated apoptosis via the TLR2/JNK pathway. Immunohistochemistry showed that CLIC1 was present in the cytoplasm of carcinoma cells, and that the very strong or very weak expression of CLIC1 was an independent poor prognostic factor. Conclusions: The present results suggest that the very strong expression of CLIC1 enhances tumor survival, while its very weak expression promotes cellular movement. The present study provides an insight into the role of CLIC1 as a switch among tumor behaviors in ESCC.

Highlights

Chloride intracellular channel 1 (CLIC1) is one of the CLIC family proteins, and was initially found to be overexpressed in activated macrophages [1]
In order to elucidate the functions of chloride intracellular channel 1 (CLIC1) in esophageal squamous cell carcinoma (ESCC), we investigated 9 cell lines for CLIC1 protein expression
TE5 and KYSE70 cell lines (Figure 2A). These results indicate that CLIC1 has a critical function in controlling the proliferation and survival of ESCC cells

Summary

Introduction

Chloride intracellular channel 1 (CLIC1) is one of the CLIC family proteins, and was initially found to be overexpressed in activated macrophages [1]. Recent studies revealed that CLIC1 is expressed in various cancers, and plays crucial roles in multiple cell functions including control of the cell cycle, apoptosis, proliferation, invasiveness, and metastasis [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24]. The expression and role of CLIC1 in human esophageal squamous cell carcinoma (ESCC) remains unknown. Recent studies have reported important roles for chloride intracellular channel 1 (CLIC1) in various cancers; its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. The present study provides an insight into the role of CLIC1 as a switch among tumor behaviors in ESCC

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