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The mechanism of malignant transformation of CADM1-positive lung adenocarcinoma

Research Project

Project/Area Number 25460432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionJichi Medical University (2015-2016)
The University of Tokyo (2013-2014)

Principal Investigator

Matsubara Daisuke  自治医科大学, 医学部, 准教授 (80415554)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsCADM1 / RAPGEF2 / RAP1 / non-TRU type / lung adenocarcinoma / RAPGE2 / EMT / 肺腺癌 / PRMT5
Outline of Final Research Achievements

Some invasive high-grade adenocarcinomas overexpress CADM1. Here, we investigated the characteristics of CADM1-positive high-grade subtype. In this study, we found that lung adenocarcinoma cell lines expressing CADM1 frequently show low level expressions of bronchial epithelial markers. Furthermore, these CADM1-positive cell lines co-express RAPGEF2. Knockdown of RAPGEF2 reduced cell migration and RAP1 activity, which suggested that RAPGEF2 promoted cell migration through activation of RAP1. In addition, our knockdown experiments of RAPGEF2 indicate that RAPGEF2 reduces the tumor suppressor function of CADM1. Immunohistochemical analysis of lung adenocarcinoma cases (n=140) revealed that high level expression of RAPGEF2 correlated with high-grade subtype, low level expressions of bronchial epithelial markers, and worse prognosis especially in CADM1-positive lung adenocarcinomas. In conclusion, RAPGEF2 will get involved in the malignant phenotype of CADM1-positive high grade subtype.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Remarks (5 results)

  • [Journal Article] Identification of cell-type-specific mutations in nodal T-cell lymphomas.2017

    • Author(s)
      Nguyen TB, Sakata-Yanagimoto M, Asabe Y, Matsubara D, Kano J, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Izutsu K, Nakamura N, Takeuchi K, Miyoshi H, Ohshima K, Minowa T, Ogawa S, Noguchi M, Chiba S.
    • Journal Title

      Blood Cancer Journal

      Volume: 7 Issue: 1 Pages: e516-e516

    • DOI

      10.1038/bcj.2016.122

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pancreatic neuroendocrine tumor with metastasis to the spleen: a case report.2017

    • Author(s)
      Sakuma Y, Yasuda Y, Sata N, Hosoya Y, Shimizu A, Fujii H, Matsubara D, Fukushima N, Miki A, Maeno M, Lefor AK.
    • Journal Title

      BMC Cancer

      Volume: 17 Issue: 1 Pages: 37-37

    • DOI

      10.1186/s12885-016-3020-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Crohn's disease presenting as a ceco-urachal fistula.2017

    • Author(s)
      Tsukui H, Koinuma K, Morimoto M, Horie H, Lefor AK, Kagaya Y, Takahashi H, Yano T, Matsubara D, Yamamoto H, Sata N.
    • Journal Title

      Clin J Gastroenterol

      Volume: 10 Issue: 1 Pages: 32-36

    • DOI

      10.1007/s12328-016-0691-2

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 胸部の原発不明癌の鑑別2017

    • Author(s)
      松原 大祐
    • Journal Title

      病理と臨床

      Volume: 35 Pages: 152-159

    • Related Report
      2016 Annual Research Report
  • [Journal Article] p53 is a Host Cell Regulator during Herpes Simplex Encephalitis.2016

    • Author(s)
      Maruzuru Y, Koyanagi N, Takemura N, Uematsu S, Matsubara D, Suzuki Y, Arii J, Kato A, Kawaguchi Y.
    • Journal Title

      J Virol.

      Volume: 90(15) Issue: 15 Pages: 6738-6745

    • DOI

      10.1128/jvi.00846-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of YAP1 defines neuroendocrine differentiation of lung tumors.2016

    • Author(s)
      Ito T, Matsubara D, Tanaka I, Makiya K, Tanei ZI, Kumagai Y, Shiu SJ, Nakaoka HJ, Ishikawa S, Isagawa T, Morikawa T, Shinozaki-Ushiku A, Goto Y, Nakano T, Tsuchiya T, Tsubochi H, Komura D, Aburatani H, Dobashi Y, Nakajima J, Endo S, Fukayama M, Sekido Y, Niki T, Murakami Y.
    • Journal Title

      Cancer Science

      Volume: 107 Issue: 10 Pages: 1527-1538

    • DOI

      10.1111/cas.13013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion2016

    • Author(s)
      Ikenoue T, Terakado Y, Nakagawa H, Hikiba Y, Fujii T, Matsubara D, Noguchi R, Zhu C, Yamamoto K, Kudo Y, Asaoka Y, Yamaguchi K, Ijichi H, Tateishi K, Fukushima N, Maeda S, Koike K, Furukawa Y
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 23899-23899

    • DOI

      10.1038/srep23899

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Frequent loss of the expression of multiple subunits of the SWI/SNF complex in large cell carcinoma and pleomorphic carcinoma of the lung.2015

    • Author(s)
      Yoshimoto T, Matsubara D, Nakano T, Tamura T, Endo S, Sugiyama Y, Niki T.
    • Journal Title

      Pathology international

      Volume: 35 Issue: 11 Pages: 595-602

    • DOI

      10.1111/pin.12350

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma2015

    • Author(s)
      Shin Saito, Kazue Morishima, Takashi Ui, Hiroko Hoshino, Daisuke Matsubara, Shumpei Ishikawa, Hiroyuki Aburatani, Masashi Fukayama, Yoshinori Hosoya, Naohiro Sato, Alan K Lefor, Yoshikazu Yasuda and Toshiro Niki
    • Journal Title

      BMC cancer

      Volume: 15 Issue: 1 Pages: 1-12

    • DOI

      10.1186/s12885-015-1065-8

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical analysis of the expression of E-cadherin and ZEB1 in non-small cell lung cancer.2014

    • Author(s)
      Matsubara D, Kishaba Y, Yoshimoto T, Sakuma Y, Sakatani T, Tamura T, Endo S, Sugiyama Y, Murakami Y, Niki T
    • Journal Title

      Pathology International

      Volume: 64 Issue: 11 Pages: 560-568

    • DOI

      10.1111/pin.12214

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition.2014

    • Author(s)
      Ibrahim R, Matsubara D, Osman W, Morikawa T, Goto A, Morita S, Ishikawa S, Aburatani H, Takai D, Nakajima J, Fukayama M, Niki T, Murakami Y
    • Journal Title

      Hum Pathol.

      Volume: 45 Issue: 7 Pages: 1397-405

    • DOI

      10.1016/j.humpath.2014.02.013

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stromal fibroblasts are predictors of disease-related mortality in esophageal squamous cell carcinoma.2014

    • Author(s)
      Saito S, Morishima K, Ui T, Matsubara D, Tamura T, Oguni S, Hosoya Y, Sata N, Lefor AT, Yasuda Y, Niki T.
    • Journal Title

      Oncology Reports

      Volume: 32 Issue: 1 Pages: 348-354

    • DOI

      10.3892/or.2014.3216

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 高悪性度神経内分泌腫瘍におけるYAP1 の欠失は,神経内分泌分化と薬剤感受性を決定づける2016

    • Author(s)
      松原 大祐
    • Organizer
      第57回 日本肺癌学会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 形態学的アプローチに基づくNon-TRU type 肺腺癌の解析:TFF-1 とTTF-1 の相互排他的な関係性について2016

    • Author(s)
      松原 大祐
    • Organizer
      第57回 日本肺癌学会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Inactivating mutations of the NKX2-1 gene in non-TRU-type lung cancer:identification through histology-driven approach2016

    • Author(s)
      松原 大祐
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] The role of RAPGEF2 in CADM1-positive high-grade lung adenocarcinoma.2015

    • Author(s)
      Shu-Jen Shiu, Daisuke Matsubara, Teppei Morikawa, KJun Nakajima, Masashi Fukayama, Toshiro Niki, Yoshinori Murakami
    • Organizer
      74th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Nagoya Congress Center (Nagoya)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Loss of YAP1 defines neuroendocrine differentiation of lung tumor.2015

    • Author(s)
      Matsubara D, Ito T, Tanaka I, Makiya K, Kumagai Y, Sue J, Shumpei I, Isagawa T, Morikawa T, Ushiku A, Goto Y, Nakano T, Tsuchiya T, Aburatani H, Dobashi Y, Nakajima J, Endo S, Fukayama M, Sekido Y, Niki T, and Murakami Y
    • Organizer
      74th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Nagoya Congress Center (Nagoya)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression pattern of YAP1 in primary lung adenocarcinomas; correlation with pathologic features and prognosis.2014

    • Author(s)
      2.Daisuke Matsubara, Takeshi Ito, Ichidai Tanaka, Teppei Morikawa, Jun Nakajima, Masashi Fukayama, Toshiro Niki, Yoshitaka Sekido, Yoshinori Murakami.
    • Organizer
      73th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition2014

    • Author(s)
      Matsubara D, Ibrahim RA, Osman W, Morikawa T, Morita S, Ishikawa S, Aburatani H, Fukayama M, Niki T, Murakami Y
    • Organizer
      AACR
    • Place of Presentation
      サンディエゴ、アメリカ
    • Related Report
      2013 Research-status Report
  • [Presentation] 1.Expression of PRMT5 in lung adenocarcinoma: correlation with pathologic features and prognosis2013

    • Author(s)
      Ibrahim RA, Matsubara D, Osman W, Morikawa T, Morita S, Ishikawa S, Aburatani H, Fukayama M, Niki T, Murakami Y
    • Organizer
      72th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Remarks] 自治医科大学統合病理学部門ホームページ

    • URL

      http://www.jichi.ac.jp/pathol/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 自治医大統合病理ホームページ

    • URL

      http://www.jichi.ac.jp/pathol/

    • Related Report
      2015 Research-status Report
  • [Remarks] 自治医科大学病理学講座統合病理学部門ホームページ

    • URL

      http://www.jichi.ac.jp/pathol/

    • Related Report
      2014 Research-status Report
  • [Remarks] 最近の学会発表

    • URL

      http://www.jichi.ac.jp/pathol/index.php?%E6%9C%80%E8%BF%91%E3%81%AE%E5%AD%A6%E4%BC%9A%E7%99%BA%E8%A1%A8

    • Related Report
      2013 Research-status Report
  • [Remarks] 最近の発表論文

    • URL

      http://www.jichi.ac.jp/pathol/index.php?%E6%9C%80%E8%BF%91%E3%81%AE%E7%99%BA%E8%A1%A8%E8%AB%96%E6%96%87

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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