Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer

Cancer Sci. 2018 Jan;109(1):84-93. doi: 10.1111/cas.13434. Epub 2017 Nov 22.

Abstract

Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In the present study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. Expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis. Patients with lower RacGAP1 level had a longer survival time and lower recurrence risk. Multivariate results identified the independent prognostic role of RacGAP1 for both recurrence and survival in EOC patients. Cellular studies showed that RacGAP1 can positively regulate the activation of RhoA and Erk proteins. In addition, wound healing assay and Transwell assay found that RacGAP1 can up-regulate the migration and invasion process of EOC cells, respectively. In all, our results not only confirmed the prognostic role of RacGAP1 for recurrence and survival in EOC patients, but also highlighted its possible potency for drug development.

Keywords: RacGAP1; epithelial ovarian cancer; invasion; prognosis; proliferation.

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • GTPase-Activating Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • rhoA GTP-Binding Protein / metabolism

Substances

  • GTPase-Activating Proteins
  • mgcRacGAP
  • RHOA protein, human
  • Extracellular Signal-Regulated MAP Kinases
  • rhoA GTP-Binding Protein