Elucidation of the molecular mechanism of the malignant transformation of cancer with the Wnt5a signal and development of the molecular target medicine
| Project/Area Number |
25250018
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Osaka University |
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Principal Investigator |
Kikuchi Akira 大阪大学, 医学(系)研究科(研究院), 教授 (10204827)
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| 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)
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| Project Period (FY) |
2013-10-21 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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)
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| Keywords | Wnt5a / 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 |
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| 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.
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Report
(4 results)
Research Products
(40 results)
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[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.
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Journal Title
J. Clin. Invest.
Volume: 印刷中
Related Report
Peer Reviewed
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[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.
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Journal Title
Elife
Volume: 5
Pages: 1-19
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
FASEB J.
Volume: 30
Issue: 4
Pages: 1534-1547
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Sci. Rep.
Volume: 5
Issue: 1
Pages: 10536-10536
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Sci. Rep.
Volume: 5
Issue: 1
Pages: 8042-8042
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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
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Journal Title
J. Cell Sci.
Volume: 128
Pages: 1051-1063
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
EMBO J
Volume: 33
Issue: 7
Pages: 702-718
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
PLoS One
Volume: 8
Issue: 12
Pages: e83629-e83629
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J. Cell Sci.
Volume: 126
Pages: 2931-2943
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Hepatology
Volume: (in press)
Issue: 6
Pages: 2502-2513
DOI
Related Report
Peer Reviewed
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