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Integrative analyses of lung adenocarcinomas that have undergone epithelial to mesenchymal transition (EMT) and those that retain an epithelial phenotype

Research Project

Project/Area Number 15K08364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

Sakuma Yuji  札幌医科大学, 医学部, 准教授 (10364514)

Co-Investigator(Kenkyū-buntansha) 山口 美樹  札幌医科大学, 医学部, 助教 (10530454)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肺腺癌 / 上皮間葉移行 / EGFR / 薬剤耐性 / 肺胞上皮 / TTF-1 / 幹細胞 / EGFR遺伝子変異 / 分子標的治療
Outline of Final Research Achievements

EGFR-mutant lung adenocarcinomas depend on the kinase for survival. We have identified a new molecular mechanism that contributes to TKI resistance, and a previously unrecognized membranous molecule TKI-resistant cancer cells selectively express. (1) The EGFR mutant lung adenocarcinoma cell line, H1975, has a subset of cells that exhibits an EMT phenotype and can thrive in the presence of EGFR TKIs. These cells depend on the isomerase Pin1 for survival in vitro, unlike their parental cells. (2) A mesenchymal EGFR-independent subline derived from the EGFR mutant lung adenocarcinoma cell line, HCC827, expressed ACE2 to a greater extent than its parental cells. We also developed an anti-ACE2 mouse monoclonal antibody (mAb), termed H8R64, that was internalized by ACE2-expressing cells. If an antibody-drug conjugate consisting of a humanized mAb based on H8R64 and a potent anticancer drug were produced, it could be effective for the treatment of EGFR-mutant lung adenocarcinomas.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 Other

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

  • [Journal Article] Angiotensin-converting enzyme 2 is a potential therapeutic target for EGFR-mutant lung adenocarcinoma.2017

    • Author(s)
      Yamaguchi M, Hirai S, Sumi T, Tanaka Y, Tada M, Nishii Y, Hasegawa T, Uchida H, Yamada G, Watanabe A, Takahashi H, Sakuma Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 487(3) Issue: 3 Pages: 613-618

    • DOI

      10.1016/j.bbrc.2017.04.102

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis.2017

    • Author(s)
      Yamaguchi M, Hirai S, Tanaka Y, Sumi T, Miyajima M, Mishina T, Yamada G, Otsuka M, Hasegawa T, Kojima T, Niki T, Watanabe A, Takahashi H, Sakuma Y.
    • Journal Title

      Lab Invest.

      Volume: Mar;97(3) Issue: 3 Pages: 232-242

    • DOI

      10.1038/labinvest.2016.135

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prolyl isomerase Pin1 promotes survival in EGFR-mutant lung adenocarcinoma cells with an epithelial-mesenchymal transition phenotype.2016

    • Author(s)
      Sakuma Y, Nishikiori H, Hirai S, Yamaguchi M, Yamada G, Watanabe A, Hasegawa T, Kojima T, Niki T, Takahashi H.
    • Journal Title

      Lab Invest.

      Volume: 96 Issue: 4 Pages: 391-398

    • DOI

      10.1038/labinvest.2015.155

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] EGFR変異陽性肺腺癌と特発性肺線維症の分子細胞病理学2016

    • Author(s)
      佐久間裕司
    • Organizer
      第62回日本病理学会秋期特別総会
    • Place of Presentation
      金沢市文化ホール(石川県金沢市)
    • Year and Date
      2016-11-10
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Isomerase Pin1 promotes survival in EGFR mutant lung adenocarcinoma c ells with an EMT phenotype2016

    • Author(s)
      佐久間裕司、長谷川 匡、仁木利郎
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2015 Research-status Report
  • [Remarks] 札幌医科大学医学部附属フロンティア医学研究所・分子医学部門

    • URL

      http://web.sapmed.ac.jp/molm/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 札幌医科大学医学部附属フロンティア医学研究所分子医学部門

    • URL

      http://web.sapmed.ac.jp/molm/

    • Related Report
      2016 Research-status Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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