Targeted Knockdown of IQGAP1 Inhibits the Progression of Esophageal Squamous Cell Carcinoma In Vitro and In Vivo

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.

Knockdown of IQGAP1 inhibits proliferation and epithelial–mesenchymal transition by Wnt/β-catenin pathway in thyroid cancer

“…A previous study showed that IQGAP1 knockdown results in a prominent reduction in cell proliferation and invasion in the FTC133 cells 15. As is reported in some other types of cancers,21,22 we also found that knockdown of IQGAP1 suppressed proliferation of SW579 and TPC-1 cell lines and reduced tumor growth in vivo. To explore how IQGAP1, as a multifunctional protein, regulates tumor proliferation and EMT in thyroid cancer, the regulation of IQGAP1 on the expressions of the EMT-related proteins E-cadherin, N-cadherin, Vimentin, Twist1, β-catenin and the Wnt/β-catenin targets c-myc and cyclin D1 in thyroid cancer were detected in vitro and in vivo.…”

IQGAP1 connects phosphoinositide signaling to cytoskeletal reorganization

“…IQGAP1 is upregulated in several different types of cancers [52], including hepatocellular [53,54], prostate [55], glioma [56] and breast [57] cancers. In most studies, perturbing IQGAP1 levels by upregulation or downregulation has a corresponding effect on cell migration in a variety of normal and cancer cell lines [55][56][57][58]. It was also seen that IQGAP1 promotes cell migration in an interdependent manner with PIPKIγ.…”

Human Adipocytes : Proteomic Approaches

“…IQGAP1 knock out animals show no obvious developmental defects but exhibit gastric hyperplasia [114] and reduced tumorigenesis [115]. Silencing IQGAP1 in cell lines also seems to inhibit their cancerogenic behavior [109,116].…”