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Stiff Substrates Enhances ATF5-Signaling-Mediated Invasive Ability in Cancer Cells

Research Project

Project/Area Number 26430104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionHokkaido University

Principal Investigator

HAGA HISASHI  北海道大学, 先端生命科学研究院, 教授 (00292045)

Project Period (FY) 2014-04-01 – 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 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)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん細胞 / 浸潤 / メカノセンス / 炎症性反応 / 転写調節因 / 転写調節因子
Outline of Final Research Achievements

High matrix stiffness triggers cancer progression; however, detailed molecular mechanisms of this phenomenon are not clear. Hence, it is necessary to identify transcription factors that contribute to malignant alteration in response to increasing substrate stiffness. In this study, we found that activating transcription factor 5 (ATF5) enhances the invasiveness of cancer cells. In addition, we revealed that ATF5 regulates the expression of genes encoding integrins, which are important for substrate stiffness sensing. Based on these observations, ATF5 possibly drives cancer progression due to stiff matrix. We also examined ATF5 localization on substrates with different rigidity. Matrix rigidity affects ATF5 transport to the nucleus.

Report

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

    (22 results)

All 2016 2015 2014 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 11 results,  Acknowledgement Compliant: 8 results) Presentation (9 results) Remarks (2 results)

  • [Journal Article] Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells2016

    • Author(s)
      Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
    • Journal Title

      Data in Brief

      Volume: 6 Pages: 793-798

    • DOI

      10.1016/j.dib.2015.12.053

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Conformational Plasticity of JRAB/MICAL-L2 Provides 'Law and Order'2016

    • Author(s)
      A. Sakane, S. Yoshizawa, M. Nishimura, Y. Tsuchiya, N. Matsushita, K. Miyake, K. Horikawa, I. Imoto, C. Mizuguchi, H. Saito, T. Ueno, S. Matsushita, H. Haga, S. Deguchi, K. Mizuguchi, H.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 27 Issue: 20 Pages: 3095-3108

    • DOI

      10.1091/mbc.e16-05-0332

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of ATF5 in the invasive potential of diverse human cancer cell lines2016

    • Author(s)
      Akihiro Nukuda, Hiroki Endoh, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 474(3) Issue: 3 Pages: 509-514

    • DOI

      10.1016/j.bbrc.2016.04.131

    • NAID

      120006219898

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Receptor activator of NF-κB ligand induces cell adhesion and integrin α2 expression via NF-κB in head and neck cancers2016

    • Author(s)
      T.Yamada, M. Tsuda, T. Wagatsuma, Y. Fujioka, M. Fujioka, A. O. Satoh, K. Horiuchi, S. Nishide, A. Nanbo, Y. Totsuka, H. Haga, S. Tanaka, M. Shindoh, and Y. Ohba
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 23545-23545

    • DOI

      10.1038/srep23545

    • NAID

      120005753715

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stiff Substrates Increase YAP-Signaling-Mediated Matrix Metalloproteinase-7 Expression2015

    • Author(s)
      A. Nukuda, C. Sasaki, S. Ishihara, T. Mizutani, K. Nakamura, T. Ayabe, K. Kawabata, and H. Haga
    • Journal Title

      Oncogenesis

      Volume: 4 Issue: 9 Pages: e165-e165

    • DOI

      10.1038/oncsis.2015.24

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Filamin B Enhances the Invasiveness of Cancer Cells into 3D Collagen Matrices2015

    • Author(s)
      Y. Iguchi, S. Ishihara, Y. Uchida, K. Tajima, T. Mizutani, K. Kawabata, and H. Haga
    • Journal Title

      Cell Structure and Function

      Volume: 40 Issue: 2 Pages: 61-67

    • DOI

      10.1247/csf.15001

    • NAID

      130005086307

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transgene Integration into the Human AAVS1 Locus Enhances Myosin II-Dependent Contractile Force by Reducing Expression of Myosin Binding Subunit 852015

    • Author(s)
      T. Mizutani, R. Li, H. Haga, and K. Kawabata
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 465 Issue: 2 Pages: 270-274

    • DOI

      10.1016/j.bbrc.2015.08.018

    • NAID

      120005906854

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activating Transcription Factor 5 Enhances Radioresistance and Malignancy in Cancer Cells2015

    • Author(s)
      S. Ishihara, M. Yasuda, A. Ishizu, M. Ishikawa, H. Shirato, and H. Haga
    • Journal Title

      Oncotarget

      Volume: 6 Pages: 4602-4614

    • NAID

      120005613573

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Compressive stress induces dephosphorylation of the myosin regulatory light chain via RhoA phosphorylation by the adenylyl cyclase/protein kinase A signaling pathway.2015

    • Author(s)
      Takemoto, T., Ishihara, S., Mizutani, T., Kawabata, K., Haga, H.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 3 Pages: e0117937-e0117937

    • DOI

      10.1371/journal.pone.0117937

    • NAID

      120005613567

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Leader Cells Regulate Collective Cell Migration via Rac Activation in the Downstream Signaling of Integrin Beta1 and PI3K2015

    • Author(s)
      N. Yamaguchi, T. Mizutani, K. Kawabata, and H. Haga
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 7656-7656

    • DOI

      10.1038/srep07656

    • NAID

      120005567742

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activating Transcription Factor 5 Enhances Radioresistance and Malignancy in Cancer Cells2014

    • Author(s)
      S. Ishihara, M. Yasuda, A. Ishizu, M. Ishikawa, H. Shirato, H. Haga
    • Journal Title

      Oncotarget

      Volume: 09 Jul Issue: 1 Pages: 1-8

    • DOI

      10.1007/s10616-014-9766-4

    • NAID

      120005613573

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 転写因子ATF5による多様ながん細胞株の浸潤促進2016

    • Author(s)
      温田 晃弘, 安田 元昭, 水谷 武臣, 川端 和重, 芳賀 永
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of ATF5 in cancer cell invasion of several diverse human cancer cell lines2016

    • Author(s)
      Akihiro Nukuda, Motoaki Yasuda, and Hisashi Haga
    • 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)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Fascin-1 promotes cancer cell invasion via activation of Stat32016

    • Author(s)
      Toshiki Takahashi, Akihiro Nukuda, Masayuki Kano, Hisahiro Matsubara, and Hisashi Haga
    • 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)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Activating transcription factor 5 promotes cancer cell invasion through transcriptional activation of integrins2015

    • Author(s)
      Akihiro Nukuda, Hiroki Endo, Seiichiro Ishihara, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, and Hisashi Haga
    • Organizer
      2015 Annual Meeting of the American Society for Cell Biology
    • Place of Presentation
      サンディエゴ(アメリカ合衆国)
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Activating transcription factor 5 promotes invasion of cancer cells via transcriptional activation of integrins2015

    • Author(s)
      Akihiro Nukuda, Seiichiro Ishihara, Motoaki Yasuda, and Hisashi Haga
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 基質の硬さによって促進される大腸がん細胞の悪性化: 転写因子YAPを介した基質分解酵素MMP-7の発現亢進2015

    • Author(s)
      温田 晃弘, 石原 誠一郎, 水谷 武臣, 中村 公則, 綾部 時芳, 川端 和重, 芳賀 永
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Activating transcription factor 5 enhances radioresistance and malignant phenotypes in lung cancer cells2014

    • Author(s)
      S. Ishihara, M. Yasuda, T. Nishioka, and H. Haga
    • Organizer
      第73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
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Invasive ability is regulated by activating transcription factor 5 in high invasive cancer cells2014

    • Author(s)
      H. Endoh, S. Ishihara, T. Nishioka, M. Yasuda, and H. Haga
    • Organizer
      第73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
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Substrate stiffness enhances expression of matrix metalloproteinase 7 via myosin phosphorylation in colon cancer cells2014

    • Author(s)
      A. Nukuda, S. Ishihara, K. Nakamura, T. Ayabe, and H. Haga
    • Organizer
      第73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
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Remarks]

    • URL

      http://altair.sci.hokudai.ac.jp/g3/research/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 細胞ダイナミクス科学研究室 研究紹介

    • URL

      http://altair.sci.hokudai.ac.jp/g3/research/

    • Related Report
      2015 Research-status Report 2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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