Overexpression and biological function of IQGAP3 in human pancreatic cancer.

IQGAP3 (IQ motif containing GTPase activating protein3) belongs to IQGAP family. Recent studies have investigated that IQGAP3 was overexpressed in several tumor tissues. This study was designed to explore the expression and role of IQGAP3 in pancreatic cancer, a highly lethal disease. IQGAP3 mRNA expression was significantly increased in pancreatic cancer tissues, compared with non-cancerous tissues. Moreover, its expression was strongly associated with tumor size, differentiation, lymph node metastasis and patients' overall survival. Gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) dataset showed that cell apoptosis, metastasis and Cdc42 pathways were strongly associated with IQGAP3 expression in pancreatic cancer patients. Knocking down of IQGAP3 in two pancreatic cancer cell lines with high level of IQGAP3 (BXPC-3 and SW1990) significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, silencing of IQGAP3 also affected the expression of cell apoptosis-, metastasis- and Cdc42 pathway-related proteins. Cdc42 knockdown had similar inhibitory effects on the cellular behavior of BXPC-3 cells. In conclusion, IQGAP3 may act as an oncogene in pancreatic cancer through regulating Cdc42 expression. Our data suggest IQGAP3 might be a novel diagnostic marker and therapeutic target for this cancer.