Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical outcome

Med Oncol. 2015 Feb;32(2):329. doi: 10.1007/s12032-014-0329-5. Epub 2015 Jan 14.

Abstract

Ras-related C3 botulinum toxin substrate 1 (rac1) has been implicated in tumor epithelial-mesenchymal transition (EMT); however, limited information is available regarding the role of rac1 in epithelial ovarian cancer (EOC). This study aimed to evaluate the correlation of rac1 expression with EMT and EOC prognosis. Rac1 protein levels of 150 EOC specimens were evaluated by immunohistochemical staining. Survival analysis was performed to determine the correlation between rac1 expression and survival. Cellular and molecular changes were also examined after rac1 in ovarian cancer cells was silenced in vitro and in vivo. The mechanism of rac1 on EMT was investigated by Western blot analysis. Rac1 was highly expressed in EOC. Rac1 overexpression was closely associated with advanced stage based on International Federation of Gynecology and Obstetrics, poor grade, serum Ca-125, and residual tumor size. Survival analyses demonstrated that patients with high rac1 expression levels were more susceptible to early tumor recurrence with very poor prognosis. This study revealed that rac1 downregulation decreased cell EMT and proliferation capability in vitro and in vivo. Rac1 expression possibly altered cell EMT by interacting with p21-activated kinase 1 and p38 mitogen-activated protein kinase signaling pathways. The present study showed that rac1 overexpression is associated with cell EMT and poor EOC prognosis. Rac1 possibly plays an important role in predicting EOC metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult
  • rac1 GTP-Binding Protein / biosynthesis*

Substances

  • RAC1 protein, human
  • rac1 GTP-Binding Protein