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Roles of ESCRT in Oncogenesis

Research Project

Project/Area Number 24300326
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Carcinogenesis
Research InstitutionMiyagi Prefectural Hospital Organization Miyagi Cancer Center

Principal Investigator

TANAKA NOBUYUKI  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 部長 (60280872)

Co-Investigator(Kenkyū-buntansha) OGAMA Naoko  地方独立法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 主任研究員 (30390892)
TAMAI Keiichi  地方独立法人宮城県立病院機構宮城県立がんセンター(研究所), がん幹細胞研究部, 上席主任研究員 (40509262)
Yamaguchi Kazunori  地方独立法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん研究部, 上席主任研究員 (80373215)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsESCRT / 増殖因子受容体 / 癌 / 小胞輸送 / オートファジー / プロテオーム
Outline of Final Research Achievements

Vesicular transport is tightly related with oncogenesis, malignant transformation and cell death. In the present study, we analyzed roles of ESCRT in vitro and in vivo. First, we found that ESRT-0 and ESCRT-I both regulate EGFR degradation. Second, AMSH-LP, a deubuiqutination enzyme associated with ESCRT-0 and ESCRT-III, may be involved in oncogenesis, and AMSH-LP knockout mice manifested shorter life span. Third, ESCRT-0 defect did not induce tumor formation, but cells defective for ESCRT-0 showed enhanced necroptosis and apoptosis, partly through the enhanced ER stress. Together, this study showed a pertinent role of ESCRT in cellular growth and death.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (23 results)

All 2016 2015 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 4 results,  Acknowledgement Compliant: 6 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways2016

    • Author(s)
      Oshima R, Hasegawa T, Tamai K, Sugeno N, Yoshida S, Kobayashi J, Kikuchi A, Baba T, Futatsugi A, Sato I, Satoh K, Takeda A, Aoki M and Tanaka N
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 24997-24997

    • DOI

      10.1038/srep24997

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer2014

    • Author(s)
      Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, Sato I, Takahashi S, Kondo T, Satoh K.
    • Journal Title

      Biochem Biophy Res Commun

      Volume: 436 Issue: 2 Pages: 319-324

    • DOI

      10.1016/j.bbrc.2013.05.101

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma2014

    • Author(s)
      Keiichi Tamai, Mao Nakamura, Masamichi Mizuma, Mai Mochizuki, Misa Yokoyama, Hiroyuki Endo, Kazunori Yamaguchi, Takayuki Nakagawa, Masaaki Shiina, Michiaki Unno, Koji Muramoto, Ikuro Sato, Kennichi Satoh, Kazuo Sugamura, and Nobuyuki Tanaka
    • Journal Title

      Cancer Science

      Volume: 105 Issue: 6 Pages: 667-674

    • DOI

      10.1111/cas.12406

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synergistic cytotoxicity of afatinib and cetuximab against EGFR T790M involves Rab11-dependent EGFR recycling.2014

    • Author(s)
      Watanuki, Z.Kosai, H., Osanai, N., Ogama, N., Mochizuki, M., Tamai, K., Yamaguchi, K., Satoh, K., Fukuhara, T., Maemondo, M., Ichinose, M., Nukiwa, T., Tanaka, N.
    • Journal Title

      Biochem Biophy Res Commun

      Volume: 455 Issue: 3-4 Pages: 269-276

    • DOI

      10.1016/j.bbrc.2014.11.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] K63-linked ubiquitination by E3 Ubiquitin Ligase Nedd4-1 facilitates endosomal sequestration of internalized alpha-synuclein.2014

    • Author(s)
      Sugeno N, Hasegawa T, Tanaka N, Fukuda M, Wakabayashi K, Oshima R, Konno M, Miura E, Kikuchi A, Baba T, Anan T, Nakao M, Geisler S, Aoki M, Takeda A.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 26 Pages: 18137-18151

    • DOI

      10.1074/jbc.m113.529461

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer.2014

    • Author(s)
      Abue, M., Yokoyama, M., Shibuya, R., Tamai, K., Yamaguchi, K., Sato, I., Tanaka, N., Hamada, S., Shimosegawa, T., Sugamura, K., Satoh, K.
    • Journal Title

      Int J Oncol

      Volume: 10 Issue: 2 Pages: 1-9

    • DOI

      10.3892/ijo.2014.2743

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation2014

    • Author(s)
      Kojima, K., Amano, Y., Yoshino, K., Tanaka, N., Sugamura, K., Takeshita, T.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 48 Pages: 33296-33310

    • DOI

      10.1074/jbc.m114.578245

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hepatocyte Growth Factor Regulated Tyrosine Kinase Substrate in the peripheral development and function of B-cells2014

    • Author(s)
      Nagata T, Murata K, Murata R, Sun S-L, Saito Y, Yamaga S, Tanaka N, Tamai K, Moriya K, Kasai N, Sugamura K, and Ishii N.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 443 Issue: 2 Pages: 351-356

    • DOI

      10.1016/j.bbrc.2013.11.029

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD271 Defines a Stem Cell-Like Population in Hypopharyngeal Cancer2013

    • Author(s)
      Imai T
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e62002-e62002

    • DOI

      10.1371/journal.pone.0062002

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer.2013

    • Author(s)
      Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K.
    • Journal Title

      PlosONE

      Volume: 8 Issue: 10 Pages: e77070-e77070

    • DOI

      10.1371/journal.pone.0077070

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma2012

    • Author(s)
      Inoue D, Suzuki T, Mitsuishi Y, Miki Y, Suzuki S, Sugawara S, Watanabe M, Sakurada A, Endo C, Uruno A, Sasano H, Nakagawa T, Satoh K, Tanaka N, Kubo H, Motohashi H, Yamamoto M
    • Journal Title

      Cancer Sci

      Volume: 103 Issue: 4 Pages: 760-766

    • DOI

      10.1111/j.1349-7006.2012.02216.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced susceptibility to colitis-associated colon carcinogenesis in mice Ia eking plasma membrane-associated sialidase.2012

    • Author(s)
      Yamaguchi K, Shiozaki K, Moriya S, Koseki K, Wada T, Tateno H, Sato l, Asano M, Iwakura y Miyagi T.
    • Journal Title

      PLoS One

      Volume: 7

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway2012

    • Author(s)
      Tamai K, Shiina M, Tanaka N, Nakano T, Yamamoto A, Kondo Y, Kakazu E, Inoue J, Fukushima K, Sano K, Ueno Y, Shimosegawa T, Sugamura K.
    • Journal Title

      Virology

      Volume: 22(2) Issue: 2 Pages: 377-85

    • DOI

      10.1016/j.virol.2011.11.009

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] CD271 defines a cancer initiating cell population in hypopharyngeal cancer2015

    • Author(s)
      Nobuyuki Tanaka, Takayuki Imai, Mai Mochizuki, Sayuri Sugawara, Keiichi Tamai, Kazunori Yamaguchi, Kennichi Satoh and Kazuo Sugamura
    • Organizer
      AACR2015
    • Place of Presentation
      米国ペンシルバニア州フィラデルフィア
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PDX model for Head and Neck Cancer reveals2014

    • Author(s)
      Tanaka, N.
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CD271 plays critical roles in invading cancer cells in hypopharyngeal carcinoma2014

    • Author(s)
      Mochizuki, M. Tamai, K., Tanaka, N.
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] BEX2 plays critical roles for maintaining dormant cancer stem cells2014

    • Author(s)
      Tamai, K. Mochizuki, M. Tanaka, N.
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 下咽頭がん幹細胞マーカーCD271の同定2014

    • Author(s)
      望月麻衣, 今井隆之, 玉井恵一, 佐藤郁郎, 山口壹範, 佐藤賢一, 菅村和夫, 田中伸幸
    • Organizer
      日本細菌学会東北支部会
    • Place of Presentation
      仙台市
    • Year and Date
      2014-08-22 – 2014-08-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Combining Afatinib and Cetuximab synergistically increases their cytotoxicity for EGFR T790M-harboring cells2014

    • Author(s)
      Nobuyuki Tanaka, Zenta Watanuki, Tatsuro Fukuhara, Makoto Maemondo.
    • Organizer
      AACR Annual Meeting 2014
    • Place of Presentation
      米国カリフォルニア州サンディエゴ市
    • Year and Date
      2014-04-05 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nedd4 controls cell migration by regulating PDGF receptor signaling2013

    • Author(s)
      Nobuyuki Tanaka
    • Organizer
      American Association of Cancer Research 2013
    • Place of Presentation
      Washington DC,USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 下咽頭癌における新規がん幹細胞表面マーカー”CD271”の同定2013

    • Author(s)
      今井隆之、玉井恵一、山口壱範、佐藤郁郎、佐藤賢一、松浦一登、西條茂、菅村和夫、田中伸幸
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] BEX2は胆管癌細胞株においてがん幹細胞様の性質を制御する2013

    • Author(s)
      玉井恵一、中村真央、望月麻衣、小鎌直子、山口壱範、横山美沙、佐藤賢一、菅村和夫、田中伸幸
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] The molecular insights into degradation of ErbB32012

    • Author(s)
      Funaki, Tanaka, N., ほか
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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