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The metabolic function of RB in controlling mevalonate (MVA) pathway regulates tumor progression

Research Project

Project/Area Number 25830076
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

SASAKI Nobuari  金沢大学, がん進展制御研究所, 博士研究員 (40415170)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsコレステロール / メバロン酸経路 / 悪性進展 / 細胞内ROS / RB / 前立腺がん / 癌幹細胞 / コレステロールエステル / retinoblastoma / がん幹細胞 / ROS / cholesterol / mevalonate pathway / cancer stem cell
Outline of Final Research Achievements

Recent advances in cancer metabolism have revealed that metabolic abnormalities in cancer cells are closely related to enhanced cell proliferation and malignant progression of a number of tumors.
Mutations in Retinoblastoma (RB) gene are found at the initiation of limited human cancers, whereas RB protein inactivation is frequently found in much wider variety of cancers mainly during their progression. These findings suggest that RB exerts more roles than previously thought. Here we show that RB affects transcription of many enzymes involved in Mevalonate (MVA) pathway. We demonstrate that RB depletion in prostate cancer cells induces some of typical malignant features including tumor sphere forming-activity and hormone-refractory growth. Cholesterol and its derivatives generated by MVA pathway contribute to these phenotypes through modifying cellular ROS level.
These results indicate that RB regulates cancer progression through the metabolic function in controlling MVA pathway.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (22 results)

All 2015 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) Remarks (1 results)

  • [Journal Article] Undifferentiated State Induced by Rb-P53 Double Inactivation in Mouse Thyroid Neuroendocrine Cells and Embryonic Fibroblasts2015

    • Author(s)
      Kitajima S, Kohno S, Kondoh A, Sasaki N, Nishimoto Y, Li F, Mohammed MS, Muranaka H, Nagatani N, Suzuki M, Kido Y, Takahashi C
    • Journal Title

      STEM CELLS

      Volume: - Issue: 5 Pages: 1657-1669

    • DOI

      10.1002/stem.1971

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ATM mediates pRB function to control DNMT1 protein stability and DNA methylation.2013

    • Author(s)
      Shamma A, Suzuki M, Hayashi N, Kobayashi M, Sasaki N, Nishiuchi T, Doki Y, Okamoto T, Kohno S, Muranaka H, Kitajima S, Yamamoto K, Takahashi C
    • Journal Title

      Molecular and Cellular Biology

      Volume: 33 Issue: 16 Pages: 3113-3124

    • DOI

      10.1128/mcb.01597-12

    • NAID

      120005312327

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] RBによるメバロン酸経路を介したがん悪性進展制御機構2015

    • Author(s)
      佐々木信成, 村中勇人, 北嶋俊輔, 河野晋, Shamma A, 髙橋智聡
    • Organizer
      日本癌学会シンポジウム / 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
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] がん抑制遺伝子RBによるSREBP-1の制御とがんにおける役割の解析2015

    • Author(s)
      村中勇人, 北嶋俊輔, 佐々木信成, 河野晋, 林昭夫, 多田秀明, 丹下正一郎, 鈴木健人, Shamma A, 髙橋智聡
    • Organizer
      日本癌学会シンポジウム / 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
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] The metabolic function of RB in controlling mevalonate (MVA) pathway regulates tumor progression2015

    • Author(s)
      Sasaki N, Kitajima S, Muranaka H, Shamma A, Kohno S, Takahashi C
    • Organizer
      Keyston Symposia
    • Place of Presentation
      Fairmont Hotel Vancouver, Vancouver, Canada
    • Year and Date
      2015-01-13 – 2015-01-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] RBによるメバロン酸経路を介したがん悪性進展制御機構2014

    • Author(s)
      佐々木信成, 村中勇人, 北嶋俊輔, 河野晋, Shamma A, 髙橋智聡
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] がん抑制遺伝子RBによるSREBP-1の制御とがんにおける役割の解析2014

    • Author(s)
      村中勇人, 北嶋俊輔, 佐々木信成, 河野晋, 吉田晶代, 丹下正一朗, 鈴木健之, 林昭夫, 多田秀昭, Shamma A, 髙橋智聡
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] RBの中心代謝制御機能2014

    • Author(s)
      河野晋, 北嶋俊輔, 吉田晶代, 鈴木佐和子, 田中知明, 佐々木信成, 村中勇人, 髙橋智聡
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The metabolic function of RB in controlling mevalonate (MVA) pathway and tumor progression2014

    • Author(s)
      Sasaki N, Muranaka H, Kitajima S, Kohno S, Shamma A and Takahashi C
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] RBによるメバロン酸経路を介したがん悪性進展制御機構2014

    • Author(s)
      佐々木信成, 村中勇人, 北嶋俊輔, 河野晋, Shamma A, 髙橋智聡
    • Organizer
      平成26年度 がん若手研究者ワークショップ
    • Place of Presentation
      蓼科 蓼科グランドホテル滝の湯
    • Year and Date
      2014-09-03 – 2014-09-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] がん抑制遺伝子RBによるSREBP-1の制御とがんにおける役割の解析2014

    • Author(s)
      村中勇人, 北嶋俊輔, 佐々木信成, 河野晋, Shamma A, 髙橋智聡
    • Organizer
      平成26年度 がん若手研究者ワークショップ
    • Place of Presentation
      蓼科 蓼科グランドホテル滝の湯
    • Year and Date
      2014-09-03 – 2014-09-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] RB不活性化によって誘導されるがん幹細胞様未分化状態におけるPgam2の役割2014

    • Author(s)
      河野晋, 北嶋俊輔, 佐々木信成, 村中勇人, 鈴木佐和子, 田中知明, 岡橋伸幸, 松田史生, 清水浩, 髙橋智聡
    • Organizer
      第2回がんと代謝研究会
    • Place of Presentation
      東京 東京理科大学葛飾キャンパス 図書館大ホール
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] The metabolic function of RB in controlling mevalonate (MVA) pathway and cancer cells2014

    • Author(s)
      Nobunari Sasaki, Chiaki Takahashi
    • Organizer
      International Symposium on Tumor Biology in Kanazawa & Symposium on Drug Discovery in Academics
    • Place of Presentation
      金沢 エクセルホテル東急
    • Related Report
      2013 Research-status Report
  • [Presentation] RB controls lipid metabolism in cancer cells2014

    • Author(s)
      Hayato Muranaka, Shunsuke Kitajima, Nobunari Sasaki, Susumu Kohno, Awad Shamma, Chiaki Takahashi
    • Organizer
      International Symposium on Tumor Biology in Kanazawa & Symposium on Drug Discovery in Academics
    • Place of Presentation
      金沢 エクセルホテル東急
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of RB tumor suppressor gene in central carbon metabolism2014

    • Author(s)
      Susumu Kohno, Shunsuke Kitajima, Sawako Suzuki, Tomoaki Tanaka, Nobuyuki Okahashi, Fumio Matsuda, Hiroshi Shimizu, Nobunari Sasaki, Hayato Muranaka, Chiaki Takahashi
    • Organizer
      International Symposium on Tumor Biology in Kanazawa & Symposium on Drug Discovery in Academics
    • Place of Presentation
      金沢 エクセルホテル東急
    • Related Report
      2013 Research-status Report
  • [Presentation] RBの中心炭素代謝調節機能2013

    • Author(s)
      河野晋、北嶋俊輔、佐々木信成、村中勇人、鈴木佐和子、田中知明、岡橋信幸、松田史生、清水浩、高橋智聡
    • Organizer
      第1回がんと代謝研究会
    • Place of Presentation
      鶴岡 慶應義塾大学先端生命科学研究所
    • Related Report
      2013 Research-status Report
  • [Presentation] The role of RB tumor suppressor gene in central carbon metabolism2013

    • Author(s)
      Susumu Kohno, Shunsuke Kitajima, Nobunari Sasaki, Hayato Muranaka, Chiaki Takahashi
    • Organizer
      Third International Rb Meeting
    • Place of Presentation
      Monterey, CA. USA
    • Related Report
      2013 Research-status Report
  • [Presentation] がん抑制遺伝子RBの代謝調節機能2013

    • Author(s)
      河野晋、北嶋俊輔、佐々木信成、村中勇人、高橋智聡
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] The pRB-ATM-DNMT1 nexus is a novel pathway to the epigenetic control of cancer progression2013

    • Author(s)
      Awad Shamma, Naoyuki Hayashi, Nobunari Sasaki, Chiaki Takahashi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] RBによるメバロン酸経路の制御とがん幹細胞における役割2013

    • Author(s)
      佐々木信成、高橋智聡
    • Organizer
      平成25年度がん若手ワークショップ
    • Place of Presentation
      蓼科 蓼科グランドホテル滝の湯
    • Related Report
      2013 Research-status Report
  • [Presentation] The metabolic function of RB tumor suppressor gene2013

    • Author(s)
      Susumu Kohno, Shunsuke Kitajima, Nobunari Sasaki, Hayato Muranaka, Chiaki Takahashi
    • Organizer
      American Association for Cancer Research Annual Meeting 2013
    • Place of Presentation
      Washington, DC. USA
    • Related Report
      2013 Research-status Report
  • [Remarks] 金沢大学がん進展制御研究所 腫瘍分子生物学研究分野 高橋智聡研究室

    • URL

      http://omb.w3.kanazawa-u.ac.jp/

    • Related Report
      2014 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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