Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo
IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thor...
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| Published in | PloS one Vol. 9; no. 5; p. e96501 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Public Library of Science
06.05.2014
Public Library of Science (PLoS) |
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| Abstract | IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy. |
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| AbstractList | IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy. IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy. |
| Audience | Academic |
| Author | Wang, Xiao-Xia Jing, Li-Wei Liu, Zhi-Rong An, Qi-Jun Wang, Xu-Hong Wang, Kang Li, Xiao-Zhong Wang, Hui-Zhen Zhai, Li-Qin Qu, Chong-Xiao Zhao, Yan |
| AuthorAffiliation | 4 Department of Statistics, Shanxi Medical University, Taiyuan, China Vanderbilt University, United States of America 1 Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China 3 Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, China 5 Department of Surgery, Shanxi Cancer Hospital, Taiyuan, China 2 Department of Emergency, Shanxi Provincial People's Hospital, Taiyuan, China |
| AuthorAffiliation_xml | – name: 2 Department of Emergency, Shanxi Provincial People's Hospital, Taiyuan, China – name: 4 Department of Statistics, Shanxi Medical University, Taiyuan, China – name: 3 Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, China – name: 1 Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China – name: Vanderbilt University, United States of America – name: 5 Department of Surgery, Shanxi Cancer Hospital, Taiyuan, China |
| Author_xml | – sequence: 1 givenname: Xiao-Xia surname: Wang fullname: Wang, Xiao-Xia organization: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China – sequence: 2 givenname: Kang surname: Wang fullname: Wang, Kang organization: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China – sequence: 3 givenname: Xiao-Zhong surname: Li fullname: Li, Xiao-Zhong organization: Department of Emergency, Shanxi Provincial People's Hospital, Taiyuan, China – sequence: 4 givenname: Li-Qin surname: Zhai fullname: Zhai, Li-Qin organization: Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, China – sequence: 5 givenname: Chong-Xiao surname: Qu fullname: Qu, Chong-Xiao organization: Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, China – sequence: 6 givenname: Yan surname: Zhao fullname: Zhao, Yan organization: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China – sequence: 7 givenname: Zhi-Rong surname: Liu fullname: Liu, Zhi-Rong organization: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China – sequence: 8 givenname: Hui-Zhen surname: Wang fullname: Wang, Hui-Zhen organization: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China – sequence: 9 givenname: Qi-Jun surname: An fullname: An, Qi-Jun organization: Department of Emergency, Shanxi Provincial People's Hospital, Taiyuan, China – sequence: 10 givenname: Li-Wei surname: Jing fullname: Jing, Li-Wei organization: Department of Statistics, Shanxi Medical University, Taiyuan, China – sequence: 11 givenname: Xu-Hong surname: Wang fullname: Wang, Xu-Hong organization: Department of Surgery, Shanxi Cancer Hospital, Taiyuan, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24800852$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2014 Public Library of Science 2014 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2014 Wang et al 2014 Wang et al |
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| Notes | Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: XXW XZL. Performed the experiments: XXW KW XZL YZ. Analyzed the data: XXW KW XZL LQZ CXQ ZRL LWJ. Contributed reagents/materials/analysis tools: XXW HZW QJA XHW. Wrote the paper: XXW. |
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doi: 10.1002/1097-0215(200002)9999:9999<::AID-IJC1121>3.0.CO;2-Z contributor: fullname: H Takemoto – volume: 10 start-page: 125 year: 2010 ident: ref18 article-title: IQGAP1 and IQGAP2 are reciprocally altered in hepatocellular carcinoma publication-title: BMC Gastroenterol doi: 10.1186/1471-230X-10-125 contributor: fullname: CD White – volume: 12 start-page: 540 year: 2013 ident: ref20 article-title: Overexpression of IQGAP1 in human pancreatic cancer publication-title: Hepatobiliary Pancreat Dis Int doi: 10.1016/S1499-3872(13)60085-5 contributor: fullname: XX Wang – volume: 42 start-page: 477 year: 2010 ident: ref19 article-title: IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation publication-title: Exp Mol Med doi: 10.3858/emm.2010.42.7.049 contributor: fullname: F Chen – volume: 281 start-page: 832 year: 1998 ident: ref27 article-title: Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin- 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| SubjectTerms | Animal tissues Animals Biochemistry Biology and life sciences Biotechnology Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell adhesion & migration Cell growth Cell Line, Tumor Cell migration Cell Movement - genetics Cell Proliferation - genetics Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - pathology Chemotherapy Development and progression Disease Progression Epithelial-Mesenchymal Transition - genetics Esophageal cancer Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Esophageal Squamous Cell Carcinoma Esophagus Gastric cancer Gene expression Gene Expression Regulation, Neoplastic - genetics Humans IQGAP1 protein Liver cancer Lung Neoplasms - genetics Lung Neoplasms - pathology Lungs Lymph nodes Lymph Nodes - pathology Male Medicine and Health Sciences Mesenchyme Metastases Mice Mice, Inbred BALB C Molecular biology Neoplasm Invasiveness - genetics Neoplasm Invasiveness - pathology Pancreatic cancer Proteins Radiation therapy ras GTPase-Activating Proteins - genetics Research and Analysis Methods Reversion Ribonucleic acid RNA RNA-mediated interference Scaffolding Signaling Squamous cell carcinoma Stomach cancer Surgery Tumorigenesis Xenografts |
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| Title | Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo |
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