Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo

• Published in: PloS one Vol. 9; no. 5; p. e96501
• Main Authors: Wang, Xiao-Xia, Wang, Kang, Li, Xiao-Zhong, Zhai, Li-Qin, Qu, Chong-Xiao, Zhao, Yan, Liu, Zhi-Rong, Wang, Hui-Zhen, An, Qi-Jun, Jing, Li-Wei, Wang, Xu-Hong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.05.2014; Public Library of Science (PLoS)
• Subjects: 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; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096501

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.