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Studies on digestive system cancer metastasis using mouse models

Research Project

Project/Area Number 25253022
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKyoto University

Principal Investigator

TAKETO Makoto  京都大学, 医学(系)研究科(研究院), 特命教授 (70281714)

Co-Investigator(Kenkyū-buntansha) KAKIZAKI Fumihiko  京都大学, 大学院医学研究科, 特定研究員 (00609076)
SONOSHITA Masahiro  京都大学, 大学院医学研究科, 准教授 (80511857)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥46,280,000 (Direct Cost: ¥35,600,000、Indirect Cost: ¥10,680,000)
Fiscal Year 2015: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2014: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2013: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Keywords消化器がん / 浸潤 / 転移 / 予後マーカー / AES / NOTCH / ABL / TRIO / がん / 消化器 / ケモカイン / Notchシグナル / TGF-betaシグナル / 予後診断 / がん転移
Outline of Final Research Achievements

(1)In the invasion and metastasis model where mouse colon cancer cells are disseminated to the liver from spleen, we found two phase reaction of the host bone marrow-derived cells. In the early phase, neutrophils are recruited and in the late phase, fibrocytes. MMP9 and MMP2 are produced by these types of cells, respectively, which is critical for cancer invasion and metastasis.
(2)One of the genes induced by Notch signaling transcription in colon cancer cells is DAB1 of which product is tyrosine-phosphrylated by ABL kinase, which receiprocally activates ABL autophosphorylation. As a result, TRIO Y2681 is phosphorylated, which shows a strong correlation with poor prognosis as a novel diagnostic marker.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Products Report
  • Research Products

    (28 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Book (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 3 results)

  • [Journal Article] Loss of SMAD4 Promotes Colorectal Cancer Progression by Accumulation of Myeloid-Derived Suppressor Cells through the CCL15-CCR1 Chemokine Axis2016

    • Author(s)
      Susumu Inamoto1, Yoshiro Itatani1,2, Takamasa Yamamoto1, Sachiko Minamiguchi3, Hideyo Hirai4, Masayoshi Iwamoto1, Suguru Hasegawa1, Makoto Mark Taketo1,2, Yoshiharu Sakai1, and Kenji Kawada1,*
    • Journal Title

      Clin. Cancer Res.

      Volume: 22 Issue: 2 Pages: 492-501

    • DOI

      10.1158/1078-0432.ccr-15-0726

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY22016

    • Author(s)
      Kakizaki F, Sanoshita M, Miyoshi H, Itatani Y, Ito S, Kawada K, Sakai Y and Taketo MM
    • Journal Title

      Cancer Science

      Volume: 107 Issue: 11 Pages: 1622-1631

    • DOI

      10.1111/cas.13063

    • Related Report
      Products Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promotion of Colorectal Cancer Invasion and Metastasis Through Activation of Notch-Dab1-Abl-RhoGEF Protein Trio.2015

    • Author(s)
      Sonoshita M, Itatani Y, Kakizaki F, Sakimura K, Terashima T, Katsuyama Y, Sakai Y, Taketo MM.
    • Journal Title

      Cancer Discov.

      Volume: 5 Issue: 2 Pages: 198-211

    • DOI

      10.1158/2159-8290.cd-14-0595

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Aes nuclear foci in colorectal cancer cells2015

    • Author(s)
      Yoshiro Itatani1,2, Masahiro Sonoshita1, Fumihiko Kakizaki1, Katsuya Okawa3, Stefano Stifani4, Hideaki Itoh5, Yoshiharu Sakai2 and M. Mark Taketo1,2,*
    • Journal Title

      J. Biochem.

      Volume: 159 Issue: 1 Pages: 133-140

    • DOI

      10.1093/jb/mvv077

    • NAID

      40020725723

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone.2015

    • Author(s)
      Tu X, Delgado-Calle J, Condon KW, Maycas M, Zhang H, Carlesso N, Taketo MM, Burr DB, Plotkin LI, Bellido T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 112 Issue: 5

    • DOI

      10.1073/pnas.1409857112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Suppressing TGFβ signaling in regenerating epithelia in an inflammatory microenvironment is sufficient to cause invasive intestinal cancer.2015

    • Author(s)
      Oshima H, Nakayama M, Han TS, Naoi K, Ju X, Maeda Y, Robine S, Tsuchiya K, Sato T, Sato H, Taketo MM, Oshima M.
    • Journal Title

      Cancer Res.

      Volume: 75 Pages: 766-776

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antitumor activity of the MEK inhibitor trametinib on intestinal polyp formation in ApcΔ716 mice involves stromal COX-2.2015

    • Author(s)
      Fujishita T, Kajino-Sakamoto R, Kojima Y, Taketo MM, Aoki M.
    • Journal Title

      Cancer Science

      Volume: 5(予定) Issue: 6 Pages: 692-699

    • DOI

      10.1111/cas.12670

    • NAID

      120005767023

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis2014

    • Author(s)
      Hirai H, Fujishita T, Kurimoto K, Miyachi H, Kitano S, Inamoto S, Itatani Y, Saitou M, Maekawa T, Taketo MM
    • Journal Title

      Clin Exp Metastasis

      Volume: 31 Issue: 8 Pages: 977-989

    • DOI

      10.1007/s10585-014-9684-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1+ myeloid cells and facilitate liver metastasis.2013

    • Author(s)
      Itatani Y, Kawada K, Fujishita T, Kakizaki F, Hirai H, Matsumoto T, Iwamoto M, Inamoto S, Hatano E, Hasegawa S, Maekawa T, Uemoto S, Sakai Y, Taketo MM
    • Journal Title

      Gastroenterol

      Volume: 145(5) Issue: 5 Pages: 1064-1075

    • DOI

      10.1053/j.gastro.2013.07.033

    • NAID

      120005348333

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY22017

    • Author(s)
      柿崎 文彦
    • Organizer
      日本癌学会学術総会 Cancer Science Young Scientist Award
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2017-09-28
    • Related Report
      Products Report
  • [Presentation] Promotion of Colorectal Cancer Invasion and Metastasis through Activation of Notch-Dab1-Abl-RhoGEF Protein Trio2015

    • Author(s)
      Masahiro Sonoshita1 , Yoshiro Itatani1,2 , Fumihiko Kakizaki1 and Yoshiharu Sakai2, M. Mark Taketo1,2
    • Organizer
      AACR Tumor Metastasis Meeting
    • Place of Presentation
      Austin, TX, USA
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大腸がんの転移機構の解明とその臨床応用の可能性2015

    • Author(s)
      武藤 誠
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Promotion of Colorectal Cancer Invasion and Metastasis through Activation of Notch Signaling2015

    • Author(s)
      M. Mark Taketo
    • Organizer
      The Notch Meeting (Athens)
    • Place of Presentation
      Athens, Greece
    • Year and Date
      2015-10-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Promotion of colon cancer invasion and metastasis via activation of Notch-Dab1-Abl-RhoGEF protein Trio2015

    • Author(s)
      M. Mark Taketo
    • Organizer
      AACR Annual Meeting (米国癌学会総会)
    • Place of Presentation
      Philadelphia, PA, USA
    • Year and Date
      2015-04-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「大腸がん転移の分子機構と臨床応用」2015

    • Author(s)
      武藤 誠
    • Organizer
      大阪成人病センター OMCC Seminar
    • Place of Presentation
      大阪市 大阪成人病センター
    • Year and Date
      2015-03-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] “Molecular mechanisms of colon cancer metastasis: toward clinical applications”2015

    • Author(s)
      M. Mark Taketo
    • Organizer
      Brupbacher Symposium
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2015-01-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] “Role of Notch signaling in colon cancer metastasis”2014

    • Author(s)
      M. Mark Taketo
    • Organizer
      Japan Notch Meeting
    • Place of Presentation
      大阪大学、大阪市吹田市
    • Year and Date
      2014-12-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] “Role of Notch signaling in colon cancer metastasis and invasion”2014

    • Author(s)
      M. Mark Taketo
    • Organizer
      AACR Annual Meeting (米国癌学会総会)
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2014-04-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] CCL15-CCR1 axisによる大腸癌肝転移機序と、CCR1阻害薬による肝転移抑制への期待2013

    • Author(s)
      板谷喜朗、河田健二、藤下晃章、柿崎文彦、平位秀世、松本卓也、波多野悦朗、坂井義治,上本伸二、武藤誠
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 転写因子Rbpjを介したNotch シグナルによる大腸がん転移の促進2013

    • Author(s)
      園下将大, 武藤 誠
    • Organizer
      第22回 日本がん転移学会学術集会、総会
    • Place of Presentation
      松本市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Mechanism of colon cancer metastasis2013

    • Author(s)
      Makoto Mark Taketo
    • Organizer
      Frontiers in Cancer Science
    • Place of Presentation
      Singapore
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Loss of Smad4 in Colorectal Cancer Cells Promotes CCL15 Expression to Recruit CCR1+ Myeloid Cells and Facilitate Liver Metastasis.2013

    • Author(s)
      Yoshiro Itatani,Kawada K, Fujishita T, Kakizaki F, Hirai H, Matsumoto T, Iwamoto M, Inamoto S, Hatano E, Hasegawa S, Maekawa T, Uemoto S, Sakai Y, Taketo MM
    • Organizer
      American College of Surgeons
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of Notch signaling in colon cancer invasion and metastasis2013

    • Author(s)
      Makoto Mark Taketo
    • Organizer
      The Notch Meeting
    • Place of Presentation
      Athens, Greece
    • Related Report
      2013 Annual Research Report
  • [Book] ワインバーグ「がんの生物学」第二版2016

    • Author(s)
      武藤 誠・青木 正博 訳
    • Publisher
      南江堂
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] Methods fro Determining Prognosis of Cancer2015

    • Inventor(s)
      Makoto Taketo, Masahiro Sonoshita, Yoshiharu Sakai, Kennji Kawada, Yoshiro Itatani
    • Industrial Property Rights Holder
      Kyoto University
    • Filing Date
      2015-11-13
    • Acquisition Date
      2018-01-09
    • Related Report
      Products Report
    • Overseas
  • [Patent(Industrial Property Rights)] METHODS FOR DETERMINING PROGNOSIS OF CANCER2014

    • Inventor(s)
      武藤誠、園下将大、坂井義治、河田健二、板谷喜朗
    • Industrial Property Rights Holder
      武藤誠、園下将大、坂井義治、河田健二、板谷喜朗
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-06-03
    • Related Report
      2014 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] METHOD FOR DETERMINING PROGNOSIS OF CANCER2013

    • Inventor(s)
      武藤誠、園下将大、坂井義治、河田健二、板谷喜朗
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-05-16
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] Methods for Determining Prognosis of Cancer

    • Inventor(s)
      Makoto Taketo Masahiro Sonoshita, Yoshiharu Sakai, Kenji Kawada, Yoshiro Itatani
    • Industrial Property Rights Holder
      Kyoto Univeristy
    • Description
      2016-526147(公開) 2016-0103133(公開) 105264381(公開) 2997378(公開) 2912526(出願) 2015/11/13 2015/11/13 2015/11/11 2015/11/16 2015/11/13
    • Related Report
      Products Report
    • Overseas

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Published: 2013-05-15   Modified: 2019-07-29  

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