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Elucidation of the molecular mechanism of the malignant transformation of cancer with the Wnt5a signal and development of the molecular target medicine

Research Project

Project/Area Number 25250018
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionOsaka University

Principal Investigator

Kikuchi Akira  大阪大学, 医学(系)研究科(研究院), 教授 (10204827)

Co-Investigator(Kenkyū-buntansha) FUMOTO KATSUMI  大阪大学, 大学院医学系研究科, 助教 (40467783)
MATSUMOTO SHINJI  大阪大学, 大学院医学系研究科, 特任助教 (20572324)
Project Period (FY) 2013-10-21 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2015: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2014: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2013: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
KeywordsWnt5a / Wntシグナル / がん / 炎症 / エンドサイトーシス / サイトカイン / 炎症性腸疾患 / エンドサイト―シス / シグナル伝達 / 癌 / 転移 / ハイスループットスクリーニング
Outline of Final Research Achievements

This project focused on the molecular actions of Wnt5a, a representative ligand for the β-catenin-independent pathway, which has been implicated in various adult diseases including cancer. We obtained following results. 1) In polarized epithelial cells, Wnt5a and its receptor were trafficked to the basolateral region to regulate the formation of inner cavity of cysts by promoting cell-extracellular matrix attachment. 2) Wnt5a-dependent cancer cells invasion was depend on receptor-mediated endocytosis, but not and Wnt5a-dependent cancer cells proliferation was. 3) We developed a high throughput screening system to detect Wnt5a-dependent signal effectively and identified two chemical compounds for the inhibition of Wnt5a signaling. 4) Wnt5a signal enhanced interleukin-12 production in dendritic cells to promote Th1 immune-response in colorectal inflammation. These results suggest that Wnt5a signaling could be a novel therapeutic target for cancer and inflammation disease.

Report

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

    (40 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 16 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Department of Physiology/School of Medicine/Southern Illinois University(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Wnt-Myb pathway suppresses KIT expression to control the timing of salivary proacinar differentiation and duct formation.2016

    • Author(s)
      Matsumoto, S., Kurimoto, T., Taketo, M., Fujii, S., and Kikuchi, A.
    • Journal Title

      Development

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CKAP4 is involved in tumor progression as a Dickkopf1 receptor.2016

    • Author(s)
      Kimura, H., Fumoto, K., Shojima, K., Nojima, S., Osugi, Y., Tomihara, H., Eguchi, H., Shintani, Y., Endo, E., Inoue, M., Doki, Y., Okumura, M., Morii, E., and Kikuchi, A.
    • Journal Title

      J. Clin. Invest.

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin.2016

    • Author(s)
      Mihara, E., Hirai, H., Yamamoto, H., Tamura-Kawakami, K., Matano, M., Kikuchi, A., Sato, T., and Takagi, J.
    • Journal Title

      Elife

      Volume: 5 Pages: 1-19

    • DOI

      10.7554/elife.11621

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] WNT5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical WNT signaling.2016

    • Author(s)
      Abedini, A., Zamberlam, G., Lapointe, E., Tourigny, C., Boyer, A., Paquet, M., Hayashi, K., Honda, H., Kikuchi, A., Price, C., and Boerboom, D.
    • Journal Title

      FASEB J.

      Volume: 30 Issue: 4 Pages: 1534-1547

    • DOI

      10.1096/fj.15-280313

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis.2015

    • Author(s)
      Sato, A., Kayama, H., Shojima, K., Matsumoto, S., Koyama, H., Minami, Y., Nojima, S., Morii, E., Honda, H., Takeda, K., Kikuchi, A.
    • Journal Title

      Sci. Rep.

      Volume: 5 Issue: 1 Pages: 10536-10536

    • DOI

      10.1038/srep10536

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The P2Y2 receptor promotes Wnt3a and EGF-induced epithelial tubular formation of IEC6 cells by binding to integrins.2015

    • Author(s)
      Ibuka, S., Matsumoto, S., Fujii, S., Kikuchi, A.
    • Journal Title

      J Cell Sci.

      Volume: 128(11) Issue: 11 Pages: 2156-2168

    • DOI

      10.1242/jcs.169060

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt5a promotes cancer cell invasion and proliferation by receptor-mediated endocytosis-dependent and -independent mechanisms, respectively2015

    • Author(s)
      Shojima, K., Sato, A., Hanaki, H., Tsujimoto, I., Nakamura, M., Hattori, K., Sato, Y., Dohi, K., Hirata, M., Yamamoto, H., and Kikuchi, A.
    • Journal Title

      Sci. Rep.

      Volume: 5 Issue: 1 Pages: 8042-8042

    • DOI

      10.1038/srep08042

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A. Basolateral secretion of Wnt5a in polarized epithelial cells is required for apical lumen formation2015

    • Author(s)
      Yamamoto, H., Awada, C., Matsumoto, S., Kaneiwa, T., Sugimoto, T., Takao, T., and Kikuchi
    • Journal Title

      J. Cell Sci.

      Volume: 128 Pages: 1051-1063

    • DOI

      10.1242/jcs.163683

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The P2Y2 receptor promotes Wnt3a and EGF-induced epithelial tubular formation of IEC6 cells by binding to integrins2015

    • Author(s)
      Ibuka, S., Matsumoto, S., Fujii, S., and Kikuchi, A.
    • Journal Title

      J. Cell Sci.

      Volume: In press

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Arl4c expression in colorectal and lung cancers promotes tumorigenesis and may represent a novel therapeutic target2015

    • Author(s)
      Fujii, S., Matsumoto, S., Nojima, S. Morii, E., and Kikuchi, A.
    • Journal Title

      Oncogene

      Volume: In press Issue: 37 Pages: 4834-4844

    • DOI

      10.1038/onc.2014.402

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures.2014

    • Author(s)
      Matsumoto, S., Fujii, S., Sato, A., Ibuka, S., Kagawa, Y., Ishii, M., and Kikuchi, A.
    • Journal Title

      EMBO J

      Volume: 33 Issue: 7 Pages: 702-718

    • DOI

      10.1002/embj.201386942

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.2014

    • Author(s)
      Kagawa Y, Matsumoto S, Kamioka Y, Mimori M, Naito Y, Ishii T, Okuzaki D, Nishida N, Maeda S, Naito A, Kikuta J, Nishikawa K, Nishimura J, Haraguchi N, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Ishii H, Doki Y, Matsuda M, Kikuchi A, Mori M, Ishii M
    • Journal Title

      PLoS One

      Volume: 8 Issue: 12 Pages: e83629-e83629

    • DOI

      10.1371/journal.pone.0083629

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.2013

    • Author(s)
      Gon, H., Fumoto, K., Ku, Y., Matsumoto, S., and Kikuchi, A.
    • Journal Title

      Mol. Biol. Cell.

      Volume: 24 Issue: 23 Pages: 3764-3774

    • DOI

      10.1091/mbc.e13-07-0357

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The apical and basolateral secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by distinct mechanisms.2013

    • Author(s)
      Yamamoto, H., Awada, C., Hanaki, H., Sakane, H., Tsujimoto, I., Takahashi, Y., Takao, T., and Kikuchi, A.
    • Journal Title

      J. Cell Sci.

      Volume: 126 Pages: 2931-2943

    • DOI

      10.1242/jcs.126052

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt5a Signaling Mediates Biliary Differentiation of Fetal Hepatic Stem/Progenitor Cells2013

    • Author(s)
      Kakinuma S, Kiyohashi K, Kamiya A, Sakamoto N, Nitta S, Yamanaka H, YoshinoK, Fujiki J, Murakawa M, Kusano-Kitazume A, Shimizu H, Okamoto R, Azuma S, Nakagawa M, Asahina Y, Tanimizu N, Kikuchi A, Nakauchi H, and *WatanabeM
    • Journal Title

      Hepatology

      Volume: (in press) Issue: 6 Pages: 2502-2513

    • DOI

      10.1002/hep.26293

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Implication of Arl4c expression in tubulogenesis and tumorigenesis.2015

    • Author(s)
      Akira Kikuchi
    • Organizer
      第31回国際生物学賞記念シンポジウム
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Fine- tuning of differentiation and morphogenesis of tubular organs by Wnt signaling.2015

    • Author(s)
      Akira Kikuchi
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 上皮管腔形成研究を基盤にしたがん治療のための新規標的分子の同定2015

    • Author(s)
      菊池章
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 増殖因子シグナルによる上皮形態形成の分化と制御2015

    • Author(s)
      菊池章
    • Organizer
      第6回Molecular Cardiovascular Conference Ⅱ
    • Place of Presentation
      ヒルトン福岡シーホーク
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Fine-tuning regulation of salivary gland morphogenesis and differentiation by Wnt signaling2015

    • Author(s)
      Akira Kikuchi
    • Organizer
      第2回国際シンポジウム「Epithelial Tubulology」
    • Place of Presentation
      北海道大学医学部フラテホール
    • Year and Date
      2015-08-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Wnt5aシグナル伝達―その異常のがんと炎症における意義―2015

    • Author(s)
      菊池章
    • Organizer
      第48回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      かがわ国際会議場
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Epithelial tubulogenesis by growth factor signaling and tumorigenesis due to its abnormality2014

    • Author(s)
      Akira Kikuchi
    • Organizer
      The 39th Annual Meeting of the Japanese Society for Investigative Dermatology.
    • Place of Presentation
      ホテル阪急エキスポパーク
    • Year and Date
      2014-12-14
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] Wnt5a signaling; its implication in cancer and inflammation2014

    • Author(s)
      Akira Kikuchi
    • Organizer
      University of Washington and Kobe University International Joint Symposium
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2014-12-05 – 2014-12-15
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] Epithelial tubular formation by a combination of growth factor signaling and tumorigenesis due to its abnormality2014

    • Author(s)
      Akira Kikuchi
    • Organizer
      14th Japanese-German Cancer Workshop
    • Place of Presentation
      Hotel Adina, Berlin, Germany
    • Year and Date
      2014-11-14 – 2014-11-16
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of tubulogenesis by growth factor signaling and its implication in tumorigenesis2014

    • Author(s)
      Akira Kikuchi
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] 増殖因子シグナルによる上皮管腔組織形成とその破綻による発がん2014

    • Author(s)
      菊池章
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] Development of epithelial tube formation by growth factor signaling and tumorigenesis due to its abnormality2014

    • Author(s)
      Akira Kikuchi
    • Organizer
      2014 KSBMB Annual Meeting
    • Place of Presentation
      COEX, Seoul, Korea
    • Year and Date
      2014-05-14 – 2015-05-16
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] 上皮管腔構造形成のメカニズムと細胞のがん化2014

    • Author(s)
      菊池章
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] 上皮管腔組織形成とその異常によるがん2014

    • Author(s)
      菊池章
    • Organizer
      山村雄一記念ライフホール開設講演会
    • Place of Presentation
      千里ライフサイエンスセンター山村雄一記念ライフホール
    • Year and Date
      2014-04-23
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Invited
  • [Presentation] 上皮管腔組織形成とその異常によるがん2014

    • Author(s)
      菊池章
    • Organizer
      愛媛大学プロテオサイエンスセンター第1回学術シンポジウム
    • Place of Presentation
      愛媛大学
    • Year and Date
      2014-03-01
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 上皮管腔組織形成とその異常によるがん2013

    • Author(s)
      菊池章
    • Organizer
      金沢がん進展制御研究所共同利用・共同研究拠点シンポジウム
    • Place of Presentation
      金沢大学
    • Year and Date
      2013-11-09
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] Wnt Signaling (Chapter8, Wnt signaling in Development and Disease)2014

    • Author(s)
      Akira Kikuchi, Shinji Matsumoto, Katsumi Fumoto, and Akira Sato.
    • Total Pages
      472
    • Publisher
      John Wiley and Sons, Inc
    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
  • [Remarks] 大阪大学 分子病態生化学

    • URL

      http://www.med.osaka-u.ac.jp/pub/molbiobc/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 分子病態生化学

    • URL

      http://www.med.osaka-u.ac.jp/pub/molbiobc/

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
  • [Patent(Industrial Property Rights)] CKAP4を標的分子とした抗腫瘍剤2016

    • Inventor(s)
      菊池章
    • Industrial Property Rights Holder
      菊池章
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-01-28
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] CKAP4を標的分子とした抗腫瘍剤2015

    • Inventor(s)
      菊池 章
    • Industrial Property Rights Holder
      菊池 章
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-02-27
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] CKAP4を標的分子とした抗腫瘍剤2015

    • Inventor(s)
      菊池 章
    • Industrial Property Rights Holder
      菊池 章
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-02-27
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒトがんにおけるArl4cの高発現と発現抑制による抗腫瘍効果の発見2014

    • Inventor(s)
      菊池 章
    • Industrial Property Rights Holder
      菊池 章
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-09-09
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒトがんにおけるArl4cの高発現と発現抑制による抗腫瘍効果の発見2014

    • Inventor(s)
      菊池 章
    • Industrial Property Rights Holder
      菊池 章
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-09-09
    • Related Report
      2013 Annual Research Report

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Published: 2013-10-24   Modified: 2022-02-02  

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