Original Article
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World J Gastroenterol. Feb 28, 2014; 20(8): 2071-2078
Published online Feb 28, 2014. doi: 10.3748/wjg.v20.i8.2071
Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway
Pan Wang, Yun Zeng, Tao Liu, Chao Zhang, Pei-Wu Yu, Ying-Xue Hao, Hua-Xin Luo, Gang Liu
Pan Wang, Department of General Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637007, Sichuan Province, China
Pan Wang, Tao Liu, Chao Zhang, Pei-Wu Yu, Ying-Xue Hao, Hua-Xin Luo, Department of General Surgery and Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
Pan Wang, Yun Zeng, Gang Liu, Sichuan Key Laboratory of Medical Imaging, North Sichuan Medical College, Nanchong 637007, Sichuan Province, China
Yun Zeng, Gang Liu, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, Fujian Province, China
Author contributions: Wang P and Zeng Y contributed equally to this work; Wang P, Zeng Y, Zhang C and Liu G conceived and designed the study; Wang P, Zeng Y, Liu T, Yu PW, Hao YX and Luo HX performed the experiments; Wang P, Zeng Y, Zhang C and Liu G analyzed the data and wrote the manuscript.
Supported by The “Eleventh Five-year Plan” for Medical Science Development of PLA, No. 06MB243; the National Natural Science Foundation of China, No. 81101101 and No. 51273165; the Key Project of Chinese Ministry of Education, No. 212149; and the Projects of Sichuan Province, No. 2010SZ0294, No. 2011JQ0032 and No. 12ZB038
Correspondence to: Chao Zhang, Professor, Department of General Surgery and Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, No. 252, Garden West Road, Shapingba District, Chongqing 400038, China. zhangchao5642@163.com
Telephone: +86-23-68754167 Fax: +86-23-68754167
Received: August 4, 2013
Revised: November 15, 2013
Accepted: December 3, 2013
Published online: February 28, 2014
Processing time: 205 Days and 19.6 Hours
Abstract

AIM: To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.

METHODS: Fluorescent probes were used to detect reactive oxygen species (ROS) in LOVO cells. Wound healing assay and transwell assay were performed to examine the migration and invasion of LOVO cells. Expression of CLIC1 mRNA and protein, p-ERK, MMP-2 and MMP-9 proteins was analyzed by reverse transcription-polymerase chain reaction and Western blot.

METHODS: H-R treatment increased the intracellular ROS level in LOVO cells. The mRNA and protein expression of CLIC1 was elevated under H-R conditions. Functional inhibition of CLIC1 markedly decreased the H-R-enhanced ROS generation, cell migration, invasion and phosphorylation of ERK in treated LOVO cells. Additionally, the expression of MMP-2 and MMP-9 could be regulated by CLIC1-mediated ROS/ERK pathway.

CONCLUSION: Our results suggest that CLIC1 protein is involved in the metastasis of colon cancer LOVO cells via regulating the ROS/ERK pathway in the H-R process.

Keywords: Colon cancer; Intracellular chloride channel 1; Hypoxia-reoxygenation; Reactive oxygen species; Extracellular signal-regulated kinase; Cancer invasion

Core tip: Hypoxia-reoxygenation (H-R) treatment increases the intracellular reactive oxygen species (ROS) level to activate the MAPK/ERK pathway, resulting in the promotion of migration and invasion in colon cancer LOVO cells. Inhibition of chloride intracellular channel 1 (CLIC1) using specific inhibitor IAA94 can markedly decrease the H-R-enhanced ROS generation, migration, invasion and phosphorylation of ERK. The results presented in the current study suggest that CLIC1 is involved in the metastasis of colon cancer LOVO cells via regulating the ROS/ERK pathway in the H-R process.