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Identification of molecular mechanisms that regulate the proliferation-migration dichotomy of cancer cells

Research Project

Project/Area Number 18H02638
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionNagoya University

Principal Investigator

Enomoto Atsushi  名古屋大学, 医学系研究科, 教授 (20432255)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords細胞遊走 / 増殖・遊走ダイコトミー / Girdin / 代謝 / 細胞周期 / 放射線療法 / DNA障害 / 細胞移動 / CD98 / 細胞運動
Outline of Final Research Achievements

The actin-binding protein Girdin is a regulator of migration of neuroblasts and cancer cells. The present study revealed that Girdin regulates the localization of the amino acid transporter complex (CD98 complex) to control the activity of mTORC1, a master regulator of cell metabolism and proliferation. We also showed the involvement of Girdin in the sensitivity of cancer cells to ulatraviolet C. These findings suggest that Girdin is involved in various processes of cancer cells including migration and metabolism and sensitivity to radiation therapies.

Academic Significance and Societal Importance of the Research Achievements

Girdin分子は以前の研究により増殖・遊走ダイコトミーの制御因子の一つであるとされていたが、今回の研究により同分子の機能多様性が明らかとなった。生体内のがん細胞も浸潤期には分裂しないことが提唱されており(stop or go hypothesis)、抗がん剤に対する抵抗性の原因とされている。今後、Girdinの多様な制御をコントロールできる手法が解明されれば、新規治療法の開発の端緒となる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(16 results)

All 2021 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Oncolytic activity of naturally attenuated herpes-simplex virus HF10 against an immunocompetent model of oral carcinoma2021

    • Author(s)
      Takano G, Esaki S, Goshima F, Enomoto A, Hatano Y, Ozaki H, Watanabe T, Sato Y, Kawakita D, Murakami S, Murata T, Nishiyama Y, Iwasaki S, Kimura H
    • Journal Title

      Molecular Therapy - Oncolytics

      Volume: 20 Pages: 220-227

    • DOI

      10.1016/j.omto.2020.12.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The balance of stromal BMP signaling mediated by GREM1 and ISLR drives colorectal carcinogenesis.2021

    • Author(s)
      Kobayashi H, Gieniec KA, Wright JA, Wang T, Asai N, Mizutani Y, Iida T, Ando R, Suzuki N, Lannagan TR, Ng JQ, Hara A, Shiraki Y, Mii S (14番目/36人中), ..., Enomoto A, Takahashi M, Worthley DL, Woods SL.
    • Journal Title

      Gastroenterology

      Volume: 160 Pages: 1224-1239

    • DOI

      10.1053/j.gastro.2020.11.011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD109 regulates in vivo tumor invasion in lung adenocarcinoma through TGF-β signaling.2020

    • Author(s)
      Taki T, Shiraki Y, Enomoto A, Weng L, Chen C, Asai N, Murakumo Y, Yokoi K, Takahashi M, Mii S.
    • Journal Title

      Cancer Science

      Volume: 111 Pages: 4616-4628

    • DOI

      10.1111/cas.14673

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complex roles of the actin-binding protein Girdin/GIV in DNA damage-induced apoptosis of cancer cells.2020

    • Author(s)
      Chen C, Enomoto A, Weng L, Taki T, Shiraki Y, Mii S, Ichihara R, Kanda M, Koike M, Kodera Y, Takahashi M.
    • Journal Title

      Cancer Sci

      Volume: 111 Pages: 4303-4317

    • DOI

      10.1111/cas.14637

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer-associated fibroblasts that restrain cancer progression: Hypotheses and perspectives2020

    • Author(s)
      Miyai Y, Esaki N, Takahashi M, Enomoto A
    • Journal Title

      Cancer Science

      Volume: 111 Pages: 1047-1057

    • DOI

      10.1111/cas.14346

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis.2019

    • Author(s)
      Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M. et al.
    • Journal Title

      Cancer Res

      Volume: 79 Pages: 5367-5381

    • DOI

      10.1158/0008-5472.can-19-0454

    • NAID

      120006786261

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction.2019

    • Author(s)
      Hara A, Kobayashi H, Asai N1, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A
    • Journal Title

      Circ Res.

      Volume: 125 Issue: 4 Pages: 414-430

    • DOI

      10.1161/circresaha.119.314806

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer-associated fibroblasts in gastrointestinal cancer2019

    • Author(s)
      Kobayashi H, Enomoto A, Woods SL, Burt AD, Takahashi M, Worthley DL
    • Journal Title

      Nature Reviews Gastroenterology & Hepatology

      Volume: 16 Pages: 282-295

    • DOI

      10.1038/s41575-019-0115-0

    • NAID

      120006711433

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex2018

    • Author(s)
      Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
    • Journal Title

      Plos Biology

      Volume: 16

    • DOI

      10.1371/journal.pbio.2005090

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure.2018

    • Author(s)
      Abudureyimu S, Asai N, Enomoto A, Weng L, Kobayashi H, Wang X, Chen C, Mii S, Takahashi M.
    • Journal Title

      Sci Rep.

      Volume: 8 Pages: 7292-7292

    • DOI

      10.1038/s41598-018-24064-0

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] CD109 deficiency induces osteopenia with an osteoporosis-like phenotype in vivo.2018

    • Author(s)
      Mii S, Hoshino A, Enomoto A, Murakumo Y, Ito M, Yamaguchi A, Takahashi M.
    • Journal Title

      Genes Cells

      Volume: 23 Pages: 590-598

    • DOI

      10.1111/gtc.12593

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] がん細胞のDNA損傷依存性細胞死におけるアクチン結合分子Girdinの役割2020

    • Author(s)
      榎本篤, Chen Chen, 滝哲郎, 高橋雅英.
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Stromal biology of cancer and its relevance in developing new anticancer therapeutics.2020

    • Author(s)
      Atsushi Enomoto
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Identification of cancer-associated fibroblasts that suppress pancreatic cancer progression2019

    • Author(s)
      Atsushi Enomoto, Yasuyuki Mizutani, Hiroki Kobayashi, Tadashi Iida, Susan L. Woods, Daniel L. Worthley, Masahide Takahashi
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cancer-restraining cancer-associated fibroblasts and their roles in tumor progression and immunity2019

    • Author(s)
      Atsushi Enomoto
    • Organizer
      Korean Cancer Association, 45th Annual Meeting and 5th International Cancer Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Heterogeneity of cancer-associated fibroblasts and its significance in tumor progression and response to thrapies.2018

    • Author(s)
      Enomoto, A, Takahashi, M.
    • Organizer
      The 6th JCA-AACR Special Joint Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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