Epigenetic regulation of IQGAP2 promotes ovarian cancer progression via activating Wnt/β-catenin signaling

Ovarian cancer is the most lethal gynecologic malignancy and most cases are diagnosed at an advanced stage with metastases; however, the molecular events supporting ovarian cancer development and progression remain poorly understood. In this study, by analysis of the genome-scale DNA methylation profiles of 8 healthy ovaries, 89 ovarian cancers and the corresponding 4 normal ovaries from The Cancer Genome Atlas, we unveiled the abnormalities in gene methylation of ovarian cancers, and found that IQGAP2 one of the most frequently altered genes, was significantly hypermethylated in ovarian cancer. There was an inverse correlation between IQGAP2 DNA methylation and mRNA expression, and IQGAP2 expression was downregulated in ovarian cancer. Further survival analysis indicated that decreased IQGAP2 was associated with a worse progression-free survival of patient with ovarian cancer, and biological function studies demonstrated that IQGAP2 inhibited ovarian cancer cell epithelial-mesenchymal transition, migration and invasion via suppression of Wnt-induced β-catenin nuclear translocation and transcriptional activity. Thus, these data identified IQGAP2 as a novel tumor suppressor for ovarian cancer to inhibit cell invasion through regulating Wnt/β-catenin signaling, and provided a new biomarker and potential therapeutic strategy for this disease.