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Novel approach to lung cancer treatment by modulating the key proliferation regulator in tissue development, Id genes

Research Project

Project/Area Number 19K17691
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Hirofumi Kiyokawa  国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (40790621)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords組織幹細胞 / 発生学 / 肺がん / 呼吸器内科学 / 肺癌 / 発生 / 細胞増殖 / 細胞分化
Outline of Research at the Start

癌細胞が示す高い増殖能・未分化性は、胎児期の未分化細胞の性質と非常に似ているが、実態としての共通性はわかっていない。本研究では胎児期の未分化細胞の増殖・分化制御メカニズムを解明することで、癌に対する新しい治療法を発見することを目的としている。方法としては単一細胞レベルでの分子情報を解析し、胎児期のマウス気管上皮未分化細胞の増殖・分化制御メカニズムを解明する。その後ヒト肺癌でもその機序が関与しているのかを調べ、研究の最終段階として癌細胞株を利用した実証を行う。本研究は胎児期の未分化細胞と癌細胞に共通する分子コンセプトを解明し、癌細胞への新たなる分子標的治療薬の開発につなげることが目的である。

Outline of Final Research Achievements

Lung cancer is the leading cause of cancer-related death worldwide. However, the detailed mechanism underlying the proliferation of tumor cells, especially squamous lung cancer cells, still remains to be answered. In this research, we successfully revealed that Id2 regulates the proliferation of basal cells, which are known to be the origin of squamous lung cancer. In addition, we also demonstrated that how Id2 gene is regulated in tracheas of embryos and adults, showing that Id2 overexpression results in the basal cell hyperplasia, which is known as a precancerous condition.

Academic Significance and Societal Importance of the Research Achievements

今回の研究結果は、難治性肺がんの一つである扁平上皮癌はId2遺伝子の過剰発現により出現することを示唆している。そのため気道上皮におけるId2遺伝子の発現を適切に制御することで、気管上皮細胞のがん化を防げることを示唆している。また肺がん細胞ではId2遺伝子が高発現していることを考えれば、Id2をターゲットした治療法が肺がん治療の新規治療として有用と考えられる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease2019

    • Author(s)
      Kiyokawa Hirofumi、Morimoto Mitsuru
    • Journal Title

      Development, Growth & Differentiation

      Volume: 62 Issue: 1 Pages: 67-79

    • DOI

      10.1111/dgd.12628

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] A Tgfb-Id2 axis regulates phase transitions of airway facultative stem cells between slow cycling and proliferation in development and regeneration2020

    • Author(s)
      Kiyokawa Hirofumi、Morimoto Mitsuru
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Id2-mediated cell cycle modulation governs the establishment and maintenance of airway facultative stem cells during development and regeneration2020

    • Author(s)
      Kiyokawa Hirofumi、Morimoto Mitsuru
    • Organizer
      Virtual Meeting: From Stem Cells to Human Development 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Single-cell RNA-seq illustrated the trajectories of basal progenitors in mouse developing trachea2019

    • Author(s)
      清川寛文
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] An inherited regulator for stemness capacity from epithelial progenitors to tissue stem cells in mice airway.2019

    • Author(s)
      清川寛文
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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