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CD133 dependent signals and microRNAs in cancer stem cells

Research Project

Project/Area Number 26462069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKagoshima University

Principal Investigator

MATSUBARA Shyuichiro  鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 准教授 (60199841)

Co-Investigator(Kenkyū-buntansha) 高尾 尊身  鹿児島大学, 医歯学総合研究科, 客員研究員 (80171411)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsCD133 / 癌幹細胞 / 膵臓癌 / マイクロRNA / 上皮間葉転換 (EMT) / Slug / HIF-1 / miR-30 / microRNA / HIF-1alpha / EMT / mTOR複合体 / シグナル伝達 / 膵癌幹細胞 / mTOR / Hedgehog / miRNA
Outline of Final Research Achievements

The molecular function of CD133 in the maintenance of cancer stem cells has not been elucidated. The CD133+ population of Capan-1 pancreatic cancer cell line exhibits cancer stem cell (CSC)-like properties. We established a CD133+ cell-rich subline from Capan-1 cells. Using this subline and the CD133 knocked down cells, we have shown that CD133 facilitates epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. The protein level of EMT regulating transcription factor Slug and the miR-30 family of microRNA level are increased in CD133+ cells, and the expression of these factors can enhance mesenchymal phenotype. In addition, the protein level of HIF-1alpha, which plays a major role in cancer cell survival and aggressiveness in hypoxia, increases in CD133+ cells and may enhance the mesenchymal phenotype.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (15 results)

  • [Journal Article] Efficient elimination of pancreatic cancer stem cells by Hedgehog/GLI inhibitor GANT61 in combination with mTOR inhibition.2016

    • Author(s)
      Miyazaki Y, Matsubara S, Qiang Ding, Tsukasa K, Yoshimitsu M, Kosai K, Takao S.
    • Journal Title

      Molecular Cancer

      Volume: 10 Issue: 1 Pages: 49-49

    • DOI

      10.1186/s12943-016-0534-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CD133 Modulate HIF-1α Expression under Hypoxia in EMT Phenotype Pancreatic Cancer Stem-Like Cells.2016

    • Author(s)
      Maeda K, Ding Q, Yoshimitsu M, Kuwahata T, Miyazaki Y, Tsukasa K, Hayashi T, Shinchi H, Natsugoe S, Takao S.
    • Journal Title

      Int J Mol Sci.

      Volume: 17 Issue: 7 Pages: 1025-1025

    • DOI

      10.3390/ijms17071025

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] miR-30 family promotes migratory and invasive abilities in CD133+ pancreatic cancer stem-like cells.2016

    • Author(s)
      Tsukasa K, Ding Q, Miyazaki 1, Matsubara S, Natsugoe S, Takao S
    • Journal Title

      Hum Cell

      Volume: 28 Issue: 3 Pages: 1-8

    • DOI

      10.1007/s13577-016-0137-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] EMT inducing signals in CD133+ pancreatic cancer cells2017

    • Author(s)
      Matsubara S, Tsukasa K, Maeda K, Ding Q, Miyazaki Y, Obara T, Matsuyama T, Takao S.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CD133陽性膵癌幹細胞様細胞においてmiR-30 familyは遊走と浸潤を促進する.2017

    • Author(s)
      政 幸一郎、丁 強、宮崎 優美、松原 修一郎、上野 祥子、小原 徹、松山 隆美、高尾 尊身
    • Organizer
      第35回 日本ヒト細胞学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] mTOR複合体1(mTORC1) および2(mTORC2)はCD133陽性膵癌細胞の幹細胞様性質に関与する.2017

    • Author(s)
      松原 修一郎、政 幸一郎、宮崎 優美、小原 徹、松山 隆美、高尾 尊身
    • Organizer
      第35回 日本ヒト細胞学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低酸素環境下におけるEMT形質を有する膵癌幹細胞様性質を持つ細胞においてCD133はHIF-1alphaの発現に関与する.2017

    • Author(s)
      前田 幸喜、丁 強、吉満 誠、桑畑 大作、宮崎 優美、政 幸一郎、林 知美、新地 洋之、夏越 祥次、高尾 尊身
    • Organizer
      第35回 日本ヒト細胞学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] mTOR複合体1(mTORC1) および2(mTORC2)はCD133陽性膵癌細胞の幹細胞様性質維持に異なる作用をもつ.2017

    • Author(s)
      松原 修一郎、政 幸一郎、小原 徹、松山 隆美、高尾 尊身
    • Organizer
      2017年度生命科学系学会合同年次大会 (ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hedgehog/GLI and mTOR signals in pancreatic cancer stem cells2016

    • Author(s)
      Matsubara, S., Miyazaki, Y., Tsukasa, K., Obara, T., Matsuyama, T., Takao, S.
    • 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)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] CD133陽性膵癌幹細胞様細胞におけるmiR-30 familyの機能 The role of miR30 family in pancreatic cancer stem-like cells2016

    • Author(s)
      政 幸一郎、丁 強、宮崎 優美、松原 修一郎、上野 祥子、小原 徹、松山 隆美、高尾 尊身
    • Organizer
      第5回 膵勉強会
    • Place of Presentation
      ホテルセントコスモ (鹿児島県・鹿児島市)
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵癌幹細胞の維持自己複製におけるmTORおよびHedgehogシグナルの機能 mTOR and Hedgehog signaling in pancreatic cancer stem cells2015

    • Author(s)
      松原 修一郎、宮崎 優美、政 幸一郎、上野 祥子、小原 徹、松山 隆美、高尾 尊身
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際展示場 (兵庫県・神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] The influence of miR-30 family to migration of a pancreatic cancer cell line, Capan-12015

    • Author(s)
      Tsukasa K, Miyazaki Y, Ueno S, Obara T, Matsubara S, Yoshimitsu M, Matsuyama T,Takao S
    • Organizer
      第73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
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] CD133+ pancreatic cancer cells promote peritumonal fibrosis2015

    • Author(s)
      Miyazaki Y, Yoshimitsu M, Tsukasa K, Matsubara S, Obara T, Matsuyama T,Takao S
    • Organizer
      第73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
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Significant signaling in KRAS downstream cascade maintaining the stem-like property of pancreatic cancer cells.2015

    • Author(s)
      Matsubara S, Miyazaki Y, Tsukasa K, Obara T, Ueno S, Matsuyama T,Takao S
    • Organizer
      第73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] Slug contributes to gemcitabine resistance through epithelial-mesenchymal transition in CD133(+) pancreatic cancer cells.2015

    • Author(s)
      Tsukasa K, Ding Q, Yoshimitsu M, Miyazaki Y, Matsubara S, Ueno S, Obara T, Matsuyama T,Takao S
    • Organizer
      第32回日本ヒト細胞学会学術集会
    • Place of Presentation
      ホテルスカイタワー (宮崎県・宮崎市)
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 膵癌幹細胞とKRAS- mTOR経路2015

    • Author(s)
      松原 修一郎、政 幸一郎、宮崎 優美、小原 徹、高尾 尊身
    • Organizer
      第4回 膵勉強会
    • Place of Presentation
      ブルーウェーブイン鹿児島 (鹿児島県鹿児島市)
    • Year and Date
      2015-03-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Not only mTORC1 but also mTORC2 are involved in the function to maintain stem-like property of pancreatic cancer cells.2014

    • Author(s)
      Matsubara S, Miyazaki Y, Tsukasa K, Obara T, Ueno S, Takao S
    • 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
    • Related Report
      2014 Research-status Report
  • [Presentation] The role of miR-30a in the highly migratory pancreatic cancer cell line2014

    • Author(s)
      Tsukasa K, Matsubara S, Miyazaki Y, Obara T, Ueno S, Takao S
    • Organizer
      第73回日本癌学会学術総会 (横浜)
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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