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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

Research Project

Project/Area Number 23791842
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionKobe 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
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsVAV1 / 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.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (4 results)

All 2013 2012 2011

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] 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 cancer2013

    • Author(s)
      Wakahashi S, Sudo T, Oka N, Ueno S, Yamaguchi S, Fujiwara K, Ohbayashi C, Nishimura R.
    • Journal Title

      Transl Res

      Volume: 162 Issue: 3 Pages: 181-190

    • DOI

      10.1016/j.trsl.2013.06.005

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] VAV1 contributes to epithelial-mesenchymal transition in epithelial ovarian cancer through the E-cadherin ubiquitination mediator HAKAI2012

    • Author(s)
      若橋宣 植野さやか 須藤保
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌 ホテルロイトン
    • Related Report
      2012 Research-status Report
  • [Presentation] 卵巣癌におけるVAV1-Rac1-PAK1シグナル経路の活性化2011

    • Author(s)
      若橋 宣
    • Organizer
      日本産婦人科学会
    • Place of Presentation
      リーガロイヤルホテル大阪、大阪国際会議場(大阪府)
    • Related Report
      2011 Research-status Report
  • [Presentation] VAV1 contributes to epithelial-mesenchymal transition in epithelial ovarian cancer through the suppression of E-cadherin2011

    • Author(s)
      若橋 宣
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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