CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways
Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remain...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Cell Physiol Biochem Press GmbH & Co KG
2018-04-01
|
Series: | Cellular Physiology and Biochemistry |
Subjects: | |
Online Access: | https://www.karger.com/Article/FullText/488822 |
id |
doaj-4652bcfadce24eb9889f7863bda56d4d |
---|---|
record_format |
Article |
spelling |
doaj-4652bcfadce24eb9889f7863bda56d4d2020-11-25T02:14:19ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-04-0146390792410.1159/000488822488822CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT PathwaysBo-pei LiYuan-tian MaoZhen WangYe-yang ChenYe WangChong-yu ZhaiBo ShiSi-yu LiuJin-lu LiuJun-qiang ChenBackground/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.https://www.karger.com/Article/FullText/488822Chloride intracellular channel 1Gastric cancerIntegrinsMAPKsAKT |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo-pei Li Yuan-tian Mao Zhen Wang Ye-yang Chen Ye Wang Chong-yu Zhai Bo Shi Si-yu Liu Jin-lu Liu Jun-qiang Chen |
spellingShingle |
Bo-pei Li Yuan-tian Mao Zhen Wang Ye-yang Chen Ye Wang Chong-yu Zhai Bo Shi Si-yu Liu Jin-lu Liu Jun-qiang Chen CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways Cellular Physiology and Biochemistry Chloride intracellular channel 1 Gastric cancer Integrins MAPKs AKT |
author_facet |
Bo-pei Li Yuan-tian Mao Zhen Wang Ye-yang Chen Ye Wang Chong-yu Zhai Bo Shi Si-yu Liu Jin-lu Liu Jun-qiang Chen |
author_sort |
Bo-pei Li |
title |
CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways |
title_short |
CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways |
title_full |
CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways |
title_fullStr |
CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways |
title_full_unstemmed |
CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways |
title_sort |
clic1 promotes the progression of gastric cancer by regulating the mapk/akt pathways |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-04-01 |
description |
Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways. |
topic |
Chloride intracellular channel 1 Gastric cancer Integrins MAPKs AKT |
url |
https://www.karger.com/Article/FullText/488822 |
work_keys_str_mv |
AT bopeili clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT yuantianmao clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT zhenwang clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT yeyangchen clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT yewang clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT chongyuzhai clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT boshi clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT siyuliu clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT jinluliu clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways AT junqiangchen clic1promotestheprogressionofgastriccancerbyregulatingthemapkaktpathways |
_version_ |
1724900432659087360 |