VAV1 represses E-cadherin expression through the transactivation of Snail and Slug: a potential mechanism for aberrant epithelial to mesenchymal transition in human epithelial ovarian cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 23791842
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kobe University
• Principal Investigator: WAKAHASHI Senn 神戸大学, 医学(系)研究科(研究院), 研究員 (80596651)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: VAV1 / 卵巣癌 / 上皮間葉移行 / E-cadherin

Outline of Final Research Achievements

We analyzed 88 samples from patients with ovarian cancer, which were divided into FIGO stages I and II, and III and IV. Prognostic analysis revealed that upregulated VAV1 expression correlated with poor prognosis in patients with early-stage ovarian cancer, but not with other clinicopathologic features. Stable overexpression of VAV1 in SKOV3 cells induced morphologic changes indicative of loss of intercellular adhesions and organized actin stress fibers. Western blotting and real-time reverse transcriptase-polymerase chain reaction demonstrated that these cells had downregulated E-cadherin, respectively. This downregulation is associated with EMT and invasive cancer. Furthermore, VAV1 overexpression in both SKOV3 and HOSE demonstrated that its upregulation of an E-cadherin transcriptional repressor, Snail and Slug, was not confined to ovarian cancer cells.Our findings suggest that VAV1 may play a role in the EMT of ovarian cancer, and may serve as a potential therapeutic target.

Free Research Field

婦人科腫瘍