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The axis of KEAP1/NRF2-PITX2-YAP contributes to the development of malignant mesothelioma

Research Project

Project/Area Number 17H07050
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Respiratory surgery
Research InstitutionIwate Medical University

Principal Investigator

Shigeeda Wataru  岩手医科大学, 医学部, 助教 (00802828)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords悪性胸膜中皮腫 / NRF2 / PITX2 / KEAP1 / 非小細胞肺がん / 中皮腫 / 抗がん薬 / 肺がん / 悪性中皮腫 / KEAP / 癌 / 細胞・組織
Outline of Final Research Achievements

In pleural mesothelioma/lung cancer, we examined whether KEAP1/NRF2-PITX2-YAP axis abnormality is involved in the formation of drug resistance to ROS-producing anticancer drugs. We examined expression panels of related molecules and hypermethylation of the promoter region of PITX2 gene. In cell lines where hypermethylation had occurred in the promoter region of PITX2, activation of the KEAP1 / NRF2 system was observed. With PITX2-inducible clone, it was confirmed that the sensitivity to the anti-cancer drug is restored. It was speculated that these ROS removal mechanisms are responsible for the reduced sensitivity of anti-cancer drugs.

Academic Significance and Societal Importance of the Research Achievements

本研究は,希少癌である胸悪性膜中皮腫の治療に際し,その抗がん薬感受性が左右非対称性の経路を決定づけるホメオボックス遺伝子PITX2のプロモーター領域の過メチル化に影響を受ける事を明らかにしたものである。難治性悪性胸膜中皮腫の開発にあたって,抗がん薬感受性低下の原因を明らかにした事は,新たな分子標的治療法の開発に有意義である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (2 results)

All 2019 2017

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

  • [Journal Article] Usefulness of a suction ball coagulation probe for hemostasis in complete VATS lobectomy for patients with non-small cell lung cancer2019

    • Author(s)
      Deguchi Hiroyuki、Tomoyasu Makoto、Shigeeda Wataru、Kaneko Yuka、Kanno Hironaga、Maeda Eri、Saito Hajime
    • Journal Title

      Surgery Today

      Volume: Epub ahead of print Issue: 7 Pages: 580-586

    • DOI

      10.1007/s00595-019-1769-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma2017

    • Author(s)
      Shigeeda W, Shibazaki M, Yasuhira S, Masuda T, Tanita T, Kaneko Y, Sato T, Sekido Y, Maesawa C.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 55 Pages: 93729-93740

    • DOI

      10.18632/oncotarget.20750

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2017-08-25   Modified: 2020-03-30  

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