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Hepatic tumor and Nrf2 activation by impaired autophagy

Research Project

Project/Area Number 26460384
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

Taguchi Keiko  東北大学, 医学系研究科, 助教 (20466527)

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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNrf2 / オートファジー / 肝腫瘍 / 肝臓 / 肝臓がん
Outline of Final Research Achievements

Autophagy is a mechanism to maintain protein quality in cells. impaired autophagy leads to Nrf2 activation through aberrant accumulation of p62 protein. Autophagy-impaired mice develop hepatic tumors. In this study, Nrf2 activation contributes to tumor formations.

Report

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

    (40 results)

All 2017 2016 2015 2014 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (24 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results) Book (3 results) Remarks (3 results)

  • [Journal Article] p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming2016

    • Author(s)
      Saito T, Ichimura Y, Taguchi K, Suzuki T, Mizushima T, Takagi K, Hirose Y, Nagahashi M, Iso T, Fukutomi T, Ohishi M, Endo K, Uemura T, Nishito Y, Okuda S, Obata M, Kouno T, Imamura R, Tada Y, Obata R, Yasuda D, Takahashi K, Fujimura T, Pi J, Lee MS, Ueno T, Ohe T, Mashino T, Wakai T, Kojima H, Okabe T, Nagano T et al.
    • Journal Title

      Nature Commun

      Volume: 7 Issue: 1 Pages: 12030-12030

    • DOI

      10.1038/ncomms12030

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of a new model rat: Nrf2 knockout rats are sensitive to aflatoxin B1 toxicity.2016

    • Author(s)
      Taguchi K, Takaku M, Egner PA, Morita M, Kaneko T, Mashimo T, Kensler TW, Yamamoto M.
    • Journal Title

      Toxicol Sci

      Volume: in press Issue: 1 Pages: 40-52

    • DOI

      10.1093/toxsci/kfw065

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells.2016

    • Author(s)
      Shinkai Y, Kimura T, Itagaki A, Yamamoto C, Taguchi K, Yamamoto M, Kumagai Y, Kaji T.
    • Journal Title

      Toxicol Appl Pharmacol

      Volume: 295 Pages: 37-46

    • DOI

      10.1016/j.taap.2016.01.020

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The transcription factor Bach2 is phosphorylated at multiple sites in murine B cells but a single site prevents its nuclear localization.2016

    • Author(s)
      Ando R, Shima H, Tamahara T, Sato Y, Watanabe-Matsui M, Kato H, Sax N, Motohashi H, Taguchi K, Yamamoto M, Nio M, Maeda T, Ochiai K, Muto A, Igarashi K.
    • Journal Title

      J Biol Chem

      Volume: 291 Pages: 1826-1840

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 肝疾患における転写因子Nrf2の機能変化2015

    • Author(s)
      田口恵子
    • Journal Title

      別冊BIO Clinica

      Volume: 4 Pages: 159-161

    • Related Report
      2015 Research-status Report
  • [Journal Article] Activation of the NRF2 pathway and its impact on the prognosis of anaplastic glioma patients.2015

    • Author(s)
      Kanamori M*, Higa T, Sonoda Y, Murakami S, Dodo M, Kitamura H, Taguchi K, Shibata T, Watanabe M, Suzuki H, Shibahara I, Saito R, Yamashita Y, Kumabe T, Yamamoto M, Motohashi H*, and Tominaga T.
    • Journal Title

      Neuro-Oncology

      Volume: 17 Issue: 4 Pages: 555-565

    • DOI

      10.1093/neuonc/nou282

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The circadian clock regulates the NRF2/ARE-mediated antioxidant defence pathway in the mouse lung.2014

    • Author(s)
      Pekovic-Vaughan V, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B, Sagami A, Taguchi K, Bechtold D, Loudon A, Yamamoto M, Chan J, van der Horst GTJ, Fukada Y, and Meng Q-J.
    • Journal Title

      Genes Dev

      Volume: 28 Issue: 6 Pages: 548-560

    • DOI

      10.1101/gad.237081.113

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Keap1 inhibition attenuates glomerulosclerosis.2014

    • Author(s)
      Miyazaki Y, Shimizu A, Pastan I, Taguchi K, Naganuma E, Suzuki T, Hosoya T, Yokoo T, Saito A, Miyata T, Yamamoto M, Matsusaka T.
    • Journal Title

      Nephrol Dial Transplant

      Volume: 29 Issue: 4 Pages: 783-791

    • DOI

      10.1093/ndt/gfu002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nrf2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice.2014

    • Author(s)
      Shirasaki K, Taguchi K, Unno M, Motohashi H, and Yamamoto M
    • Journal Title

      Hepatology

      Volume: 59 Issue: 6 Pages: 2371-2382

    • DOI

      10.1002/hep.27020

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nrf2 enhances cholangiocyte expansion in Pten-deficient livers.2014

    • Author(s)
      Taguchi K, Hirano I, Itoh T, Tanaka M, Miyajima A, Suzuki A, Motohashi H, and Yamamoto M.
    • Journal Title

      Mol. Cell. Biol.

      Volume: 34 Issue: 5 Pages: 900-913

    • DOI

      10.1128/mcb.01384-13

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Nrf2 activation-acquired Liver cancer2017

    • Author(s)
      Keiko Taguchi, Masayuki Yamamoto
    • Organizer
      Closed seminar at Profs. Bruce Freeman & Thomas Kensler’s laboratories in University of Pittsburgh
    • Place of Presentation
      Pittsburgh, USA
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 毒性学におけるNrf2欠失ラットの貢献2017

    • Author(s)
      田口恵子、山本雅之
    • Organizer
      第10回ラットリソースリサーチ研究会
    • Place of Presentation
      京都大学芝蘭会館稲盛ホール(京都)
    • Year and Date
      2017-02-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] オートファジー破綻がもたらす病態のNrf2を標的とした治療戦略2016

    • Author(s)
      田口恵子、鈴木隆史、山本雅之
    • Organizer
      第10回オートファジー研究会・第4回新学術「オートファジー」班会議
    • Place of Presentation
      NASPA ニューオータニ(新潟県越後湯沢)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] オートファジーの破綻による肝腫瘍とKeap1-Nrf2システム2016

    • Author(s)
      田口恵子、小松雅明、山本雅之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Nrf2 is a critical factor for hepatocellular adenoma in impaired autophagy2016

    • Author(s)
      Keiko Taguchi, Masaaki Komatsu, Masayuki Yamamoto
    • Organizer
      41st NAITO Conference
    • Place of Presentation
      CHATERAISE Gateaux Kingdom SAPPORO(北海道札幌)
    • Year and Date
      2016-07-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Nrf2の恒常的活性化はヘム合成阻害剤による肝毒性を軽減する2016

    • Author(s)
      田口恵子、増井紗帆、山本雅之
    • Organizer
      第43回日本毒性学会学術年会
    • Place of Presentation
      ウィンクあいち(愛知県名古屋)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] Keiko Taguchi, Masayuki Yamamoto2016

    • Author(s)
      Keiko Taguchi, Masayuki Yamamoto
    • Organizer
      Closed seminar at Prof. Amedeo Columbano laboratory in University of Cagliari
    • Place of Presentation
      Cagliari, Italy
    • Year and Date
      2016-06-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Nrf2 is a critical factor for hepatocellular adenoma in impaired autophagy2016

    • Author(s)
      Keiko Taguchi, Masaaki Komatsu, Masayuki Yamamoto
    • Organizer
      Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      Maui, USA
    • Year and Date
      2016-02-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nrf2はPten欠失による脂肪肝炎から肝臓がんの移行を促進する2015

    • Author(s)
      田口恵子、一戸理沙、山本雅之
    • Organizer
      第88回日本生化学会/第38回日本分子生物学会合同大会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] 2つのタンパク質分解系による統合的なNrf2の制御メカニズム2015

    • Author(s)
      田口恵子
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸国際会場(神戸)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Nrf2 はPten 欠失による脂肪肝炎から肝がんへの移行を促進する2015

    • Author(s)
      田口恵子、一戸理沙、山本雅之
    • Organizer
      第3回がんと代謝研究会・金沢大学がん進展制御研究所共同利用・共同研究拠点シンポジウム
    • Place of Presentation
      石川県立音楽堂交流ホール(金沢)
    • Year and Date
      2015-07-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Nrf2欠失ラットはアフラトキシンB1による肝毒性に対して脆弱である2015

    • Author(s)
      田口恵子、高久美咲、Thomas W. Kensler、山本雅之
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      石川県立音楽堂,金沢市アートホール、ホテル日航金沢(金沢)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
  • [Presentation] A new tool for toxicology: Nrf2 knockout rat2015

    • Author(s)
      Keiko Taguchi, Misaki Takaku, Masayuki Yamamoto
    • Organizer
      The 7th International Congress of Asian Society of Toxicology (ASIATOX2015)
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2015-06-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Nrf2 Knockout Rat Is Sensitive to Aflatoxin B1 Hepatotoxicity2015

    • Author(s)
      Keiko Taguchi, Misaki Takaku, Patricia A. Egner, Thomas W. Kensler, Masayuki Yamamoto
    • Organizer
      University of Pittsburgh Cancer Institute (UPCI) Scientific Retreat
    • Place of Presentation
      Pittsburgh, USA
    • Year and Date
      2015-06-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] タンパク質分解によるNrf2活性制御メカニズム2015

    • Author(s)
      田口恵子、本橋ほづみ、山本雅之
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(神戸)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Establishment and characterization of Nrf2 knockout rats2015

    • Author(s)
      Keiko Taguchi, Misaki Takaku, Masanobu Morita, Masayuki Yamamoto
    • Organizer
      2nd International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
    • Place of Presentation
      東京大学医科学研究所(白金台)(東京)
    • Year and Date
      2015-01-23 – 2015-01-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Establishment and characterization of Nrf2 knockout rats2015

    • Author(s)
      Keiko Taguchi, Misaki Takaku, Masanobu Morita, Masayuki Yamamoto
    • Organizer
      Biochemical Society-The Keap1/Nrf2 Pathway in Health and Disease
    • Place of Presentation
      Robinson College, Cambridge, UK
    • Year and Date
      2015-01-06 – 2015-01-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Nrf2の活性制御破綻がもたらす肝病態2014

    • Author(s)
      田口恵子
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-10-15
    • Related Report
      2014 Research-status Report
  • [Presentation] Liver diseases caused by perturbation of Nrf2 regulation2014

    • Author(s)
      Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Multi-step regulation of Nrf2 activity in the liver2014

    • Author(s)
      Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto
    • Organizer
      Japan/Korea Joint Symposium on Pharmaceutical Health Science and Environmental Toxicology
    • Place of Presentation
      つくば国際会議場(つくば)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 転写因子Nrf2の活性制御メカニズムと病態2014

    • Author(s)
      田口恵子、本橋ほづみ、山本雅之
    • Organizer
      若手放射線生物学研究会勉強会
    • Place of Presentation
      京都大学原子炉実験所(大阪)
    • Year and Date
      2014-08-08 – 2014-08-10
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Molecular Mechanisms and Functions of Keap1-Nrf2 system2014

    • Author(s)
      Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto
    • Organizer
      2014 International Symposium and Annual Meeting of The Korean Society for Applied Biological Chemistry
    • Place of Presentation
      Haeundae Grand Hotel (Busan, Korea)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Molecular Mechanisms and Functions of Keap1-Nrf2 system2014

    • Author(s)
      Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto
    • Organizer
      Gyeonggi Institute of Science & Technology Promotion
    • Place of Presentation
      Gyeonggi Institute of Science & Technology Promotion (Suwon, Korea)
    • Year and Date
      2014-06-19
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 肝毒性物質に応答した肝保護にはたらくNrf2の役割2014

    • Author(s)
      田口恵子、本橋ほづみ、山本雅之
    • Organizer
      日本生化学会東北支部第80回例会・シンポジウム
    • Place of Presentation
      アキタパークホテル(秋田)
    • Year and Date
      2014-05-10
    • Related Report
      2014 Research-status Report
  • [Book] Protein modifications in pathogenic dysregulation of signaling, Chapter 17 Keap1-Nrf2 regulatory system and cancer2015

    • Author(s)
      Taguchi K, Yamamoto M
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report
  • [Book] Protein modifications in pathogenic dysregulation of signaling2015

    • Author(s)
      Taguchi K, Yamamoto M
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report
  • [Book] 酸化ストレスの医学改訂第2版2014

    • Author(s)
      田口恵子、山本雅之
    • Total Pages
      444
    • Publisher
      診断と治療社
    • Related Report
      2014 Research-status Report
  • [Remarks] 東北大学大学院 医学系研究科 医化学分野

    • URL

      http://www.dmbc.med.tohoku.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東北大学 大学院医学系研究科 医化学分野

    • URL

      http://www.dmbc.med.tohoku.ac.jp/official/index.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 東北大学大学院 医学系研究科 医化学分野

    • URL

      http://www.dmbc.med.tohoku.ac.jp/official/index.html

    • Related Report
      2014 Research-status Report

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

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