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Analysis for molecular mechanism of SFN-induced lung adenocarcinoma progression

Research Project

Project/Area Number 26860230
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionUniversity of Tsukuba

Principal Investigator

Shiba Aya  筑波大学, 医学医療系, 助教 (50708427)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺腺癌 / 初期悪性化 / Stratifin / SKP1 / stratifin / リン酸化cyclin E1 / トランスジェニックマウス
Outline of Final Research Achievements

Here, we performed an in vivo and in vitro study to clarify the role of SFN and the underlying molecular mechanism in progression of lung adenocarcinoma.
First, we generated SFN-transgenic mice showing lung-specific expression of human SFN. We found that Tg -SFN developed lung tumors at a significantly higher rate than control mice.
One of the SFN-binding proteins, SKP1 is an adapter component of E3 ubiquitin ligase, forming a SCF complex. Our SKP1 IHC and previous results indicate that SFN combines with SKP1 and blocks SCF complex function. We already identified the SFN binding domain in SKP1 protein using in silico simulation, and started screening for small molecule compounds that specifically bind to SFN. Targeted therapy to block the SFN-SKP1 combination might be a new treatment strategy for patients with lung adenocarcinoma.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (4 results)

All 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Stratifin accelerates progression of lung adenocarcinoma at an early stage.2015

    • Author(s)
      Shiba-Ishii A, Kim Y, Shiozawa T, Iyama S, Satomi K, Kano J, Sakashita S, Morishita Y, Noguchi M.
    • Journal Title

      Molecular Cancer

      Volume: 14 Issue: 1 Pages: 142-142

    • DOI

      10.1186/s12943-015-0414-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Moesin overexpression is a unique biomarker of adenomyosis.2014

    • Author(s)
      Ohara R, Michikami H, Nakamura Y, Sakata A, Sakashita S, Satomi K, Shiba-Ishii A, Kano J, Yoshikawa H, Noguchi M.
    • Journal Title

      Pathol Int.

      Volume: 64 Issue: 3 Pages: 115-122

    • DOI

      10.1111/pin.12148

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunocytochemical staining for stratifin and OCIAD2 in bronchial washing specimens increases sensitivity for diagnosis of lung cancer.2014

    • Author(s)
      Itoguchi N1, Nakagawa T, Murata Y, Li D, Shiba-Ishii A, Minami Y, Noguchi M.
    • Journal Title

      Cytopathology.

      Volume: - Issue: 6 Pages: 354-361

    • DOI

      10.1111/cyt.12220

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Stratifin accelerates progression of lung adenocarcinoma at an early stage2015

    • Author(s)
      Aya Shiba-Ishii, Yunjung Kim, Toshihiro Shiozawa, Shinji Iyama, Yukio Morishita, and Masayuki Noguchi
    • Organizer
      World Conference on Lung Cancer
    • Place of Presentation
      Denver Convention Center (USA)
    • Year and Date
      2015-09-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2017-05-10  

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