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Molecular basis for the establishment of early metastatic lesion through cell adaptation

Research Project

Project/Area Number 15K14381
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionKobe University

Principal Investigator

Shimono Yohei  神戸大学, 医学研究科, 准教授 (90594630)

Research Collaborator MINAMI Hironobu  神戸大学, 大学院医学研究科, 教授
TAKAO Shintaro  神戸大学, 大学院医学研究科, 教授
CLARKE Michael  スタンフォード大学, 幹細胞医学研究所, 教授
ISOBE Taichi  スタンフォード大学, 幹細胞医学研究所, 博士研究員
MUKOHYAMA Junko  神戸大学, 大学院医学研究科, 大学院生
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords乳がん / 肝転移 / 異種移植マウス / マイクロRNA / エクソソーム
Outline of Final Research Achievements

Successful engraftment of disseminated metastatic cancer cells will require an adaptation of cancer cells to the specific microenvironments of metastasized organs. We identified the profile of microRNAs and genes specifically expressed in the early metastatic cancer cells directly isolated from the metastatic organ of human breast cancer patient-derived xenograft mice. We then analyzed the regulatory mechanism for the expression of miR-106b-25 cluster miRNAs. We also established the in vitro culture system in which primary liver cells and human breast cancer patient-derived xenograft cells were co-cultured to facilitate analyses of the adaptation of breast cancer cells to metastasized organs.

Report

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

    (38 results)

All 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 9 results,  Acknowledgement Compliant: 6 results) Presentation (19 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Remarks (3 results)

  • [Int'l Joint Research] スタンフォード大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] リエージュ大学(ベルギー)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] モンペリエがん研究所(フランス)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Glucose metabolism targeting therapy and withaferin A are effective for EGFR-TKI induced drug tolerant persisters.2017

    • Author(s)
      Kunimasa K, Nagano T, Shimono Y, Dokuni R, Kiriu T, Tokunaga S, Tamura D, Yamamoto M, Tachihara M, Kobayashi K, Satouchi M, Nishimura Y.
    • Journal Title

      Cancer Science

      Volume: 印刷中 Issue: 7 Pages: 1368-1377

    • DOI

      10.1111/cas.13266

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells2017

    • Author(s)
      Tominaga K, Shimamura T, Kimura N, Murayama T, Matsubara D, Kanauchi H, Niida A, Shimizu S, Nishioka K, Tsuji EI, Yano M, Sugano S, Shimono Y, Ishii H, Saya H, Mori M, Akashi K, Tada KI, Ogawa T, Tojo A, Miyano S, Gotoh N
    • Journal Title

      Oncogene

      Volume: 36(9) Issue: 9 Pages: 1276-1286

    • DOI

      10.1038/onc.2016.293

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hippo vs. Crab: tissue-specific functions of the mammalian Hippo pathway2017

    • Author(s)
      M. Nishio, T. Maehama, H. Goto, K. Nakatani, W. Kato, H. Omori, Y. Miyachi, H. Togashi, Y. Shimono and A. Suzuki
    • Journal Title

      Genes to Cells

      Volume: 22 Issue: 1 Pages: 6-31

    • DOI

      10.1111/gtc.12461

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting the Hippo signalling pathway for cancer treatment2016

    • Author(s)
      K. Nakatani, T. Maehama, M. Nishio, H. Goto, W. Kato, H. Omori, Y. Miyachi, H. Togashi, Y. Shimono and A. Suzuki
    • Journal Title

      J. Biochem.

      Volume: 161 Pages: 237-244

    • DOI

      10.1093/jb/mvw074

    • NAID

      40021162008

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4-phosphate in breast cancer2016

    • Author(s)
      Ijuin T, Takeuchi Y, Shimono Y, Fukumoto M, Tokuda E, Takenawa T
    • Journal Title

      Cancer Science

      Volume: 107 Issue: 7 Pages: 981-990

    • DOI

      10.1111/cas.12968

    • NAID

      120005866889

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells2016

    • Author(s)
      Mukohyama J, Shimono Y, Yamashita K, Sumi Y, Mukohara T, Minami H, Kakeji Y
    • Journal Title

      Anticancer Research

      Volume: 36 Pages: 3679-3686

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens.2016

    • Author(s)
      Mukohyama J, Iwakiri, D, Zen Y, Mukohara T, Minami H, Kakeji Y, Shimono Y.
    • Journal Title

      Oncotarget

      Volume: 31 Issue: 31 Pages: 50150-50160

    • DOI

      10.18632/oncotarget.10322

    • NAID

      120005890089

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organoid Culture of Human Cancer Stem Cells2016

    • Author(s)
      Shimono Y, Mukohyama J, Isobe T, Johnston DM, Dalerba P, Suzuki A
    • Journal Title

      Methods in Molecular Biology

      Volume: - Pages: 1-9

    • DOI

      10.1007/7651_2016_13

    • ISBN
      9781493976164, 9781493976171
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells Through the Inhibition of DCLK12016

    • Author(s)
      Sakaguchi M, Hisamori S, Oshima N, Sato F, Shimono Y, Sakai Y
    • Journal Title

      Molecular Cancer Research

      Volume: 14 Issue: 4 Pages: 354-362

    • DOI

      10.1158/1541-7786.mcr-15-0380

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Novel Nectin-mediated Cell Adhesion Apparatus Which Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development2016

    • Author(s)
      Kitayama M, Mizutani K, Maruoka M, Mandai K, Sakakibara S, Ueda Y, Komori T, Shimono Y, Takai Y
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 11 Pages: 5817-5831

    • DOI

      10.1074/jbc.m115.685917

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer2015

    • Author(s)
      Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, Kiyota N, Takao S, Kono S, Nakatsura T, Minami H
    • Journal Title

      Oncol Rep

      Volume: 33 Issue: 4 Pages: 1837-1843

    • DOI

      10.3892/or.2015.3767

    • NAID

      120005758024

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Downregulation of CXCR4 in Metastasized Breast Cancer Cells and Implication in Their Dormancy2015

    • Author(s)
      Nobutani K, Shimono Y, Mizutani K, Ueda Y, Suzuki T, Kitayama M, Minami A, Momose K, Miyawaki K, Akashi K, Azuma T, Takai Y
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: e0130032-e0130032

    • DOI

      10.1371/journal.pone.0130032

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] MicroRNA regulation of human breast cancer stem cells2015

    • Author(s)
      194.Shimono Y, Mukoyama J, Nakamura S, Minami H.
    • Journal Title

      J Clin Med

      Volume: 5 Issue: 1 Pages: 2-2

    • DOI

      10.3390/jcm5010002

    • NAID

      120005697222

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] MicroRNA Regulation of Cancer Stem Cells in Human Solid Tumors2017

    • Author(s)
      Yohei Shimono
    • Organizer
      神戸大学・ワシントン大学・オスロ大学国際合同シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2017-03-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Role of Hippo pathway in vivo2017

    • Author(s)
      Miki Suzuki, Tomohiko Maehama, Hideru Togashi, Yohei Shimono, Akira Suzuki
    • Organizer
      神戸大学・ワシントン大学・オスロ大学国際合同シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2017-03-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 早期転移乳がん幹細胞を特徴づける幹細胞性維持機構の解析2017

    • Author(s)
      下野 洋平、西村 建徳、向山 順子、鈴木 聡、後藤 典子
    • Organizer
      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
      金沢
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of Hippo pathway in vivo2016

    • Author(s)
      Miki Nishio、Hiroki Goto、Kohei Otsubo、Hideru Togashi、Yohei Shimono、Tomohiko Maehama、Akira Suzuki
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Evaluation of the risk of lymphomagenesis in xenografts by the detection of EBV BamHI W region in patient specimens2016

    • Author(s)
      Junko Mukohyama, Toru Mukohara, Hironobu Minami, Yoshihiro Kakeji, Yohei Shimono
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Selectively upregulated miR-221 regulates the clonogenicity of human colon cancer stem cells.2016

    • Author(s)
      Naoki Shibuya, Junko Mukohyama, Taichi Isobe, Hiroki Kondo, Toru Mukohara, Yoshihiro Kakeji, Hironobu Minami, Akira Suzuki, Yohei Shimono
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] The Hippo signaling Pathway: Function, Disorders, and Therapeutic Targeting2016

    • Author(s)
      Miki Nishio, Hiroki Goto, Yosuke Miyachi, Hideru Togashi, Yohei Shimono, Akira Suzuki
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 遺伝子改変動物を利用した、形態形成におけるHippo経路の機能解析2016

    • Author(s)
      田中雅人、後藤裕樹、西尾美希、中谷圭佑、前濱朝彦、富樫 英、下野洋平、鈴木 聡
    • Organizer
      第48回日本臨床分子形態学会
    • Place of Presentation
      熊本
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Upregulation of Oncogenic miR-221 in Human Colon Cancer Stem Cells2016

    • Author(s)
      Junko Mukohyama、Yohei Shimono、Toru Mukohaya、Yoshihiro Kakeji、Hironobu Minami
    • Organizer
      第14 回日本臨床腫瘍学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-07-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 臓器への潜在転移に関わるヒト乳がん幹細胞の解析2016

    • Author(s)
      下野 洋平、向山 順子、西村 建徳、磯部 大地、向原 徹、鈴木 聡、後藤 典子、南 博信
    • Organizer
      第26日本サイトメトリー学会
    • Place of Presentation
      福岡
    • Year and Date
      2016-07-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Molecular characterization of quiescence and stemness of metastatic breast cancer stem cells: implication for their therapeutic resistance.2016

    • Author(s)
      Yohei Shimono, Junko Mukohyama, Tatsunori Nishimura, Noriko Gotoh, Hironobu Minami, Akira Suzuki
    • Organizer
      第41回内藤コンファレンス
    • Place of Presentation
      札幌
    • Year and Date
      2016-07-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Molecular characterization of dormant metastatic human breast cancer stem cells.2016

    • Author(s)
      Yohei Shimono, Tatsunori Nishimura, Junko Mukohyama, Taichi Isobe, Toru Mukohara, Noriko Gotoh, Hironobu Minami
    • Organizer
      第14回 幹細胞シンポジウム
    • Place of Presentation
      兵庫
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素環境におけるMCM7とそのイントロン領域に存在するマイクロRNA-25の発現解離2016

    • Author(s)
      近藤 弘基、下野 洋平、向山 順子、鈴木 聡
    • Organizer
      第20回バイオ治療法研究会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of the proteins specific for human breast cancer stem cells2016

    • Author(s)
      Yohei Shimono
    • Organizer
      ベルギー大学訪問団シンポジウム
    • Place of Presentation
      神戸
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 転移乳がん幹細胞の制御機構のパスウエイ解析2015

    • Author(s)
      下野 洋平
    • Organizer
      平成27年度がん進展制御研究所 共同利用・共同研究拠点研究成果報告会
    • Place of Presentation
      金沢
    • Year and Date
      2015-12-07
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy2015

    • Author(s)
      Yuki Ueda, Kentaro Nobutani, Yohei Shimono, Kiyohito Mizutani*, Toshihiro Suzuki*, Midori Kitayama*, Akihiro Minami, Kenji Momose, Kohta Miyawaki, Koichi Akashi, Takeshi Azuma, Yoshimi Takai
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Effect of the xenotransplantation site on the microRNA expression of human colorectal cancer stem cells2015

    • Author(s)
      Junko Mukohyama, Yohei Shimono, Yohei Funakoshi, Toru Mukohara, Yoshihiro Kakeji, Hironobu Minami
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] miR-142 upregulates miR-150 and confers an aberrant proliferative ability to human breast cancer stem cells2015

    • Author(s)
      Yohei Shimono, Taichi Isobe, Shigeo Hisamori, Michael Clarke
    • Organizer
      第13回 幹細胞シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2015-05-29
    • Related Report
      2015 Research-status Report
  • [Presentation] Cancer stem cells and drug resistance in human breast cancers2015

    • Author(s)
      Yohei Shimono
    • Organizer
      Joint Symposium of University of Liege & Kobe University
    • Place of Presentation
      神戸
    • Year and Date
      2015-05-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 神戸大学大学院医学研究科 分子細胞生物学分野

    • URL

      http://www.med.kobe-u.ac.jp/mcb/staff/shimono.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] がん研究分野の特性等を踏まえた支援活動・研究紹介

    • URL

      http://ganshien.umin.jp/research/spotlight/shimono/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 「がん研究分野の特性等を踏まえた支援活動」の「研究紹介」で紹介されました

    • URL

      http://www.kobe-u.ac.jp/NEWS/research/2016_02_09_02.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2022-02-16  

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