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Development of therapeutic strategy for colorectal cancer by utilizing cross-talk between morphogenesis-related signaling pathways

Research Project

Project/Area Number 18591468
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

NOSHIRO Hirokazu  Kyushu University, Faculty of Medical Sciences, Contracted Research Associate (90301340)

Co-Investigator(Kenkyū-buntansha) KUBO Makoto  Kyushu University, University Hospital, Assistant Professor (60403961)
KOJIMA Masasyuki  Kyushu University, University Hospital, Assistant Professor (90380394)
MIBU Ryuichi  KYUSHU UNIVERSITY, School of Medicine, Professor (20200107)
UEKI Takashi  Kyushu University, University Hospital, Lecturer (30274468)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,870,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsColorectal cancer / Wnt signaling pathway / Hedgehog signaling pathway / Morphogenesis signaling Pathways / Glil mRNA / Theranv for colorectal cancer / Glil遺伝子 / シグナルクロストーク
Research Abstract

Based on our hypothesis " Wnt pathway and hedgehog (Hh) pathwaysuppress each other in colorectal cancel", our research aim is to develop a new therapeutic strategy that targets corosstalk between morphogenesis signaling pathways.
During this research period, following data were obtained.
1) Evaluation of activation status of Wnt pathway and Hh pathway in colorectal cancer specimens: Nuclear accumulation of b-catenin (Wnt pathway activation) and the Glil staining (BE pathway activation) level were inversely associated in the 40 colorectal cancers (P=0.014).
2) Crosstalk between Wnt pathway and Hh pathway in colorectal cancer cells: Suppression of Wnt pathway by Gill transfection in colorectal cancer cells was confirmed by lucrferase assay, western blot analysis, and immunostaining.
3) Mechanisms of crosstalk between Wnt pathway and BE pathway:
Suppression of Wnt pathway activation in Glil transfected cells was observed even in cells having mutated b-catenin.
4) BE pathway activation therapy for colorectal cancers involving Wnt pathway activation: Suppression of proliferation in Wnt pathway-activationg colorectal cancer cells by Glil transfection was confirmed by colony formation assay and three-dimensional culture system.
5) Crosstalk between Wnt pathway and BE pathway in other cancers: Crosstalk between Wnt pathway and Hh pathway was also observed in gastric cancer specimens.
Most of these data have been published in a form of peer-review manuscript.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (11 results)

All 2008 2007 2006 Other

All Journal Article (9 results) (of which Peer Reviewed: 5 results) Presentation (2 results)

  • [Journal Article] Crosstalk of Hedgehog and Wnt signaling pathways in gastric cancer2008

    • Author(s)
      Yanai K, et. al.
    • Journal Title

      Cancer Lett (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gamma-secretase in hibitors enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells2008

    • Author(s)
      Akiyoshi T, et. al.
    • Journal Title

      Gastroenterology 134

      Pages: 131-144

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gamma-secretase inhibitors enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells2008

    • Author(s)
      Akiyoshi, T, Nakamura, M, Yanai, K, Nagai, S, Wada, J, Koga, K, Nakashima, H, Sato, N, Tanaka, M, Katano, M
    • Journal Title

      Gastroenterology 134

      Pages: 131-144

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Crosstalk of Hedgehog and Wnt signaling pathways in gastric cancer2008

    • Author(s)
      Yanai K, et. al.
    • Journal Title

      Cancer Lett (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-secretase inhibitors enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells2008

    • Author(s)
      Akiyoshi T, et. al.
    • Journal Title

      Gastroenterology 134-144

      Pages: 131-144

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gli1,down-regulated in colorectal cancers,inhibits proliferation of colon cancer cells in volving Wnt signaling activation2006

    • Author(s)
      kiyoshi T, et. al.
    • Journal Title

      GUT 55

      Pages: 991-999

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Glil, down-regulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signaling activation2006

    • Author(s)
      Akiyoshi, T, Nakamura, M, Koga, K, Nakashima, H, Yao, T, Tsuneyoshi, M, Tanaka, M, Katano, M
    • Journal Title

      GUT 55

      Pages: 991-999

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Glii, down-regulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signaling activation.2006

    • Author(s)
      Akiyoshi T. et al.
    • Journal Title

      GUT 55

      Pages: 991-999

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Crosstalk of Hedgehog and Wnt signaling pathways in gastric cancer

    • Author(s)
      Yanai, K, Nakamura, M, Akiyoshi, T, Nagai, S, Wada, J, Koga, K, Noshiro, H, Nagai, E, Tsuneyoshi, M, Tanaka, M, Katano, M
    • Journal Title

      Cancer Lett (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 大腸癌と形態形成シグナル2007

    • Author(s)
      秋吉 高志
    • Organizer
      21世紀COEプログラム「大規模コホートに基づく生活習慣病研究教育」平成19年度若手研究者発表会
    • Place of Presentation
      福岡・九州大学病院地区コラボ・ステーションI
    • Year and Date
      2007-01-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Morphogenesis signal pathway and colorectal cancer 21 COE program "Frontier research and education Lifestyle-related diseases based on the large-scale2007

    • Author(s)
      Akiyoshi, T
    • Organizer
      Cohort study". Annual report for young researchers
    • Place of Presentation
      Fukuoka
    • Year and Date
      2007-01-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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