Investigation of the roles of IQGAP1 and Activated β-Catenin in epithelial ovarian cancer metastasis and patient outcome

Abstract

Epithelial ovarian cancer (EOC) represents 90% of all ovarian cancer types and is a leading cause of death among gynaecological cancers in developed countries. Despite long clinical trials performed to improve EOC screening and therapy using numerous methods such as surgery, chemotherapy and radiotherapy, only a limited overall improvement of the mortality rate has been achieved, as confirmed by statistical assessment. IQGAP1 is a multi-domain protein that contains numerous binding sites facilitating interaction with several other proteins such as β-catenin, E-cadherin and actin filaments to regulate the cytoskeletal rearrangements necessary for altered cell-cell adhesion and migration. IQGAP1 has been identified as a putative prognostic marker for tumour recurrence and survival of cancer patients. Deregulated gene and/or protein function leads to tumour progression to more aggressive and invasive disease. This progression effect has been observed in several different cancers including colon, thyroid, glioma and gastric cancer. Β-catenin is considered as integral adhesion molecule involved in cell-cell adhesion and migration. Additionally, it contributes to Wnt signalling. The aim of this study was to examine the role of numerous adhesion molecules like IQGAP1 and activated β-catenin in normal cells and in cancer cells displaying different EOC histo-types by using techniques such as Western blotting, Real Time Quantitative PCR and Immunohistochemistry. Our results showed a significantly increased expression of IQGAP1 within cancer tissues compared to benign tumours. Additionally, we were able to examine the matched primary ovarian cancer with their corresponding metastatic sites which clearly showed a significantly higher expression of IQGAP1 within the metastatic sites when compared to the primary lesion. Consistent with previous results, we observed a significantly higher IQGAP1 expression in patients with ascites at first diagnosis. Regarding activated β-catenin, significantly higher protein expression was observed within borderline ovarian tumours compared to cancers. Additionally, there was a significantly higher expression within primary ovarian sites when compared to matched metastatic sites. In conclusion, IQGAP1 has a role in EOC pathogenesis and metastasis, while activated β-catenin seems to have only a minor role in tumour metastasis and progression which supports the evidence that activated β-catenin is involved in tumour initiation rather than cancer progression.