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Antitumor Strategies via Regulation of PP6 Elevated in Colorectal Cancer Stem Cells

Research Project

Project/Area Number 21K16434
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionOkayama University of Science

Principal Investigator

Fujiwara Nobuyuki  岡山理科大学, 獣医学部, 講師 (30805875)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords大腸がん / がん幹細胞 / protein phosphatase 6 / PP6 / Protein phosphatase 6
Outline of Research at the Start

がん幹細胞は、がん組織の中に存在し、分裂して自身と同じ細胞を作り出すほか、がん細
胞を増やして腫瘍を一から構成する能力を持ち、抗がん剤や放射線に対する耐性を示す。こ
のがん幹細胞を制御することが、がんの再発や転移抑制に重要であることは明らかであるも
のの、がん幹細胞に対して真に有効な抗がん剤はほとんど存在しない。
そこで本研究課題では、大腸がん幹細胞で発現上昇しているPP6の発現調節機構の解析や活性調節因子の同定などを行い、大腸がん幹細胞の制御を可能とする新規抗がん戦略の構
築を目指す。

Outline of Final Research Achievements

The purpose of this study was to clarify the role of PP6 in cancer stem cells of colorectal cancer and to develop anti-cancer strategies targeting PP6. The results showed that PP6 expression was upregulated in colorectal cancer tissues. In addition, when PP6 expression was suppressed in colon cancer cells, colony-forming ability and tumor growth in vivo were inhibited. As a mechanism, it was observed that suppression of PP6 expression decreased the expression of cancer stem cell markers. These results suggest that PP6 is important for the maintenance of cancer stem cells.

Academic Significance and Societal Importance of the Research Achievements

本研究結果より、PP6が、がん幹細胞の維持に重要な働きをしていることが明らかになった。また、3種類存在するPP6の調節サブユニットの中でPP6R3ががん幹細胞の維持に重要であることが明らかとなった。今後は、PP6とPP6R3の結合の維持機構を明らかにすることで、がん幹細胞を標的とする抗がん戦略の構築が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results)

  • [Journal Article] Protein phosphatase 6 regulates trametinib sensitivity, a mitogen-activated protein kinase kinase (MEK) inhibitor, by regulating MEK1/2-ERK1/2 signaling in canine melanoma cells2023

    • Author(s)
      YAMAMOTO Miu、FUJIWARA Nobuyuki
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 85 Issue: 9 Pages: 977-984

    • DOI

      10.1292/jvms.23-0274

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated expression of RAB3B plays important roles in chemoresistance and metastatic potential of hepatoma cells2022

    • Author(s)
      Tsunedomi Ryouichi、Yoshimura Kiyoshi、Kimura Yuta、Nishiyama Mitsuo、Fujiwara Nobuyuki、Matsukuma Satoshi、Kanekiyo Shinsuke、Matsui Hiroto、Shindo Yoshitaro、Watanabe Yusaku、Tokumitsu Yukio、Yoshida Shin、Iida Michihisa、Suzuki Nobuaki、Takeda Shigeru、Ioka Tatsuya、Hazama Shoichi、Nagano Hiroaki
    • Journal Title

      BMC Cancer

      Volume: 22 Issue: 1 Pages: 260-260

    • DOI

      10.1186/s12885-022-09370-1

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The protein level of the tumour-promoting factor SET is regulated by cell density2022

    • Author(s)
      Kohyanagi Naoki、Kitamura Nao、Tanaka Keiko、Mizuno Takuya、Fujiwara Nobuyuki、Ohama Takashi、Sato Koichi
    • Journal Title

      The Journal of Biochemistry

      Volume: 171 Issue: 3 Pages: 295-303

    • DOI

      10.1093/jb/mvab125

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein phosphatase 6 promotes neurite outgrowth by promoting mTORC2 activity in N2a cells2021

    • Author(s)
      Kitamura Nao、Fujiwara Nobuyuki、Hayakawa Koji、Ohama Takashi、Sato Koichi
    • Journal Title

      The Journal of Biochemistry

      Volume: 170 Issue: 1 Pages: 131-138

    • DOI

      10.1093/jb/mvab028

    • NAID

      40022723382

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

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Published: 2021-04-28   Modified: 2025-01-30  

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