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2013 Fiscal Year Final Research Report

The role of mTOR signalng in colorectal cancer

Research Project

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Project/Area Number 24790382
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research Institution愛知県がんセンター(研究所) (2013)
Kyoto University (2012)

Principal Investigator

FUJISHITA Teruaki  愛知県がんセンター(研究所), 分子病態学部, 研究員 (50511870)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywords腫瘍 / マウスモデル
Research Abstract

mTORC1 signaling promotes cell growth and protein synthesis, and is frequently activated in various types of cancer. However, its involvement in the formation and progression of colorectal cancer remains unclear. This study investigated the roles of mTORC1 signaling in colorectal cancer by treating cis-Apc/Smad4 compound mutant mice, a mouse model for colon adenocarcinoma, with mTOR inhibitors. Although both the mTORC1-selective inhibitor RAD001 and the mTOR kinase inhibitor AZD8055 reduced colon cancer formation and prolonged the survival of cis-Apc/Smad4 mice, they failed to suppress the local invasion of colon cancer cells. Analysis of possible feedback loops revealed EGFR activation in colorectal cancer cells treated with the mTOR inhibitors, suggesting that the resistance to the mTOR inhibitors might have been acquired through activation of EGFR. Combination treatment with EGFR inhibitors may potentiate the efficacy of the mTOR inhibitors against colorectal cancer.

  • Research Products

    (5 results)

All 2013 2012

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) Book (2 results)

  • [Journal Article] Loss of SMAD4 from colorectal cancer cells promotes CCLl5 expression to recruit CCRl+myeloid cells and facilitate liver metastasis2013

    • Author(s)
      Yoshiro Itatani,Kenji Kawada,Teruaki Fujishita,et al
    • Journal Title

      Gastroenterology

      Pages: 1064-1075

    • DOI

      10.1053/j.gastro.2013.07.033

    • Peer Reviewed
  • [Presentation] Suppression of intestinal adenocarcinoma formation in cis Apc/Smad4 mice by the mTOR kinase inhibitor AZD80552013

    • Author(s)
      藤下晃章,武藤誠,青木正博
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2013-12-05
  • [Presentation] The mTOR kinase inhibitor AZD8055 suppresses the expansion of intestinal adenocarcinoma in cis Apc/Smad4 mice2013

    • Author(s)
      藤下晃章,武藤誠,青木正博
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2013-10-04
  • [Book] JNKシグナル伝達経路はmTORClの活性化を介してApc^<Δ7l6>マウスにおける腸管腫療形成を促進する.日本メディカルセンター. INTESTINE Vol.16 No.052012

    • Author(s)
      藤下晃章,青木正博
    • Total Pages
      471-473
  • [Book] mTORと発がん.細胞工学Vol.31 No.122012

    • Author(s)
      藤下晃章,青木正博
    • Total Pages
      1347-1354
    • Publisher
      秀潤社

URL: 

Published: 2015-06-25  

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