Inflammatory responses and cancer initiated by Wnt signal network

• Project/Area Number: 23650594
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Osaka University
• Principal Investigator: KIKUCHI Akira 大阪大学, 医学系・研究科, 教授 (10204827)
• Project Period (FY): 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: Wnt / 炎症 / がん / 転移 / 抗体療法 / Wntシグナル / Wnt5a / 腸管炎症 / DSS / LPS / IL-6 / IκB / NFκB

Research Abstract

Chronic inflammation in microenvironment has been shown to be involved in cancer. This study examined regulation of inflammatory responses by Wnt signaling, which play important roles in cancer pathogenesis. Wnt5 enhanced LPS-dependent IL-6 expression in mouse peritoneal macrophages and the inflammatory responses were reduced in macrophages prepared from Wnt5a knockout mice. The addition of dextran sodium sulfate(DSS) generated a mouse model for bowel inflammatory diseases. Wnt5a knockout mice were resistant to DSS-induced inflammation. Taken together with the observations that expression of Wnt5a is involved in aggressiveness of cancer, these results suggest that Wnt5a signaling links between inflammation and cancer.

Research Products

• [Journal Article] An Wnt5a-antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis (2012)
  • Author(s): Hanaki, H., Yamamoto, H., Sakane, H., Matsumoto, S., Ohdan, H., Sato, A., and Kikuchi, A
  • Journal Title: Mol. Cancer Ther. Volume: 11 Pages: 298-307
  • Peer Reviewed
• [Journal Article] Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling (2012)
  • Author(s): Sakane, H., Yamamoto, H., Matsumoto, S., Sato, A., and Kikuchi, A
  • Journal Title: J. Cell Sci. Volume: 125 Pages: 449-460
  • Peer Reviewed
• [Journal Article] Regulation of focal adhesion dynamics by Wnt5a signaling (2012)
  • Author(s): Matsumoto, S., and Kikuchi, A
  • Journal Title: Methods in Mol. Biol. Volume: 839 Pages: 215-227
  • Peer Reviewed
• [Journal Article] Wnt5a : its signaling, functions, and implication in diseases (2012)
  • Author(s): Kikuchi, A., Yamamoto, H., Sato, A., and Maysimoto, S
  • Journal Title: Acta physiol Volume: 204 Pages: 17-33
  • Peer Reviewed
• [Journal Article] An Wnt5a-antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis (2012)
  • Author(s): Hanaki, H., et.al.
  • Journal Title: Mol.Cancer Ther. Volume: 11 Pages: 298-307
  • Peer Reviewed
• [Journal Article] Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling (2012)
  • Author(s): Sakane, H., et.al.
  • Journal Title: J.Cell Sci. Volume: 125 Issue: 2 Pages: 449-460
  • DOI: 10.1242/jcs.091876
  • Peer Reviewed
• [Journal Article] Regulation of focal adhesion dynamics by Wnt5a signaling (2012)
  • Author(s): Matsumoto, S., et.al.
  • Journal Title: Methods Mol.Biol. Volume: 839 Pages: 215-27
  • DOI: 10.1007/978-1-61779-510-7_17
  • ISBN: 9781617795091, 9781617795107
  • Peer Reviewed
• [Journal Article] Wnt5a : its signaling, functions, and implication in diseases (2012)
  • Author(s): Kikuchi, A., et.al.
  • Journal Title: Acta Physiol. Volume: 204 Issue: 1 Pages: 17-33
  • DOI: 10.1111/j.1748-1716.2011.02294.x
  • Peer Reviewed
• [Journal Article] Insufficiency of BUBR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates (2011)
  • Author(s): Miyamoto, T., Porazinski, S., Wang, H., Borovina, A., Ciruna, B., Shimizu, A., Kajii, T., Kikuchi, A., Furutani-Seiki, M., and Matsuura, S
  • Journal Title: Hum. Mol. Genet. Volume: 20 Pages: 2058-2070
  • Peer Reviewed
• [Journal Article] The transmembrane protein Waif1/ 5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization (2011)
  • Author(s): Kagermeier-Schenk, B., Wehner, D., Ozhan-Kizil, G., Yamamoto, H., Jian Li, Kirchner, K., Hoffmann, C., Stern, P., Kikuchi, A., Schambony, A., and Weidinger, G.
  • Journal Title: Dev. Cell Volume: 21 Pages: 1129-1143
  • Peer Reviewed
• [Journal Article] MMP-10/ Stromelysin-2 Promotes Invasion of Head and Neck Cancer (2011)
  • Author(s): Deraz, E. M., Kudo, Y., Yoshida, M., Obayashi, M., Tsunematsu, T., Tani, H., Siriwardena, S., Keikhaee, M. R., Qi, G., Iizuka, S., Ogawa, I., Campisi, G., Lo Muzio, L., Abiko, Y., Kikuchi, A., Takata, T
  • Journal Title: PLoS ONE Volume: 6
  • NAID: 120005300499
  • Peer Reviewed
• [Journal Article] New insights into the mechanism of Wnt signaling pathway activation (2011)
  • Author(s): Kikuchi, A., Yamamoto, H., Sato, A., Mastumoto, S
  • Journal Title: Int. Rev. Cell. Mol. Biol Volume: 291 Pages: 21-71
  • Peer Reviewed
• [Journal Article] Insufficiency of BUBR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates (2011)
  • Author(s): Miyamoto, T., et.al.
  • Journal Title: Human Molcular Genetics Volume: 20 Issue: 10 Pages: 2058-2070
  • DOI: 10.1093/hmg/ddr090
  • Peer Reviewed
• [Journal Article] Waif1/5T4 inhibits Wnt/□-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization (2011)
  • Author(s): Kagermeier-Schenk, B., et.al.
  • Journal Title: Dev.Cell. Volume: 21 Pages: 1129-1143
  • Peer Reviewed
• [Journal Article] MMP10/stromelysin-2 promotes invasion of head and neck cancer (2011)
  • Author(s): Deraz EM, Kudo Y, Yoshida M, Tani H, Tsunematsu T, et al
  • Journal Title: PLos ONE Volume: (電子媒体) Issue: 10 Pages: e25438-e25438
  • DOI: 10.1371/journal.pone.0025438
  • Peer Reviewed
• [Journal Article] New insights into the mechanism of Wnt signaling pathway activation (2011)
  • Author(s): Kikuchi, A
  • Journal Title: Int Rev Cell Mol Biol. Volume: 291 Pages: 21-71
  • DOI: 10.1016/b978-0-12-386035-4.00002-1
  • ISBN: 9780123860354
  • Peer Reviewed
• [Presentation] Growth factor-dependent regulation of cell polarity during tubulogenesis (2011)
  • Author(s): Kikuchi, A.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] BUBR1, a mitotic spindle checkpoint regulator, plays a role of ciliogenesis in G0 phrase (2011)
  • Author(s): Miyamoto, T., Porazinski, S., Huijia, W., Shimizu, A., Kajii, T. Kikuchi, A., Furutani-Seiki, M., Shinya Matsuura, S.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Novel fuction of Dvl, a Wnt signaling molecule, in cytokinesis (2011)
  • Author(s): Fumoto, k., Kikuchi, K., Kikuchi, A.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Dissecting the novel functions of Axin and Prickle in cell polarization and directional migration (2011)
  • Author(s): Lim, Boon Cheng., Matsumoto, S., Kikuchi, A.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Wnt3a and Wnt5a regulate epithelial polarity and tubulogenesis cooperatively (2011)
  • Author(s): Matsumoto, S., Kikuchi, A.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Growth fector-dependent regulatian of cell polarity during tubulogenesis (2011)
  • Author(s): Kikuchi, A., et.al.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川県(招待講演)
  • Year and Date: 2011-12-15
• [Presentation] Wnt5a deficiency ameliorates the dextran sulfate sodium(DSS)-induced acute colitis (2011)
  • Author(s): Sato, A., Shojima, K., Koyama, H., Kikuchi, A.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] GSK3β/ Axin-1/β-catenin Complex is involved In Semaphorin3A Signaling (2011)
  • Author(s): Hida, T., Yamashita, N., Usui, H., Nakamura, F., Kikuchi, A., Goshima, Y.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] Wnt5a ; its signaling and implication in tumorigenesis (2011)
  • Author(s): Kikuchi, A., et.al.
  • Organizer: 13^<th> Japanese-German Cancer Workshop
  • Place of Presentation: 広島県(招待講演)
  • Year and Date: 2011-11-19
• [Presentation] Development of new therapeutic methods for cancer expressing Wnt5a by the use of anti-Wnt5a antibody (2011)
  • Author(s): Hanaki, H., Yamamoto, H., Kikuchi, A.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] The role of h-prune in anaplastic thyroid cancer cell migration and invasion (2011)
  • Author(s): Nambu, J., Kobayashi, T., Tashiro, H., Sugino, K., Shimamoto, F., Kikuchi, A. Ohdan, H.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] BUBR1, a mitotic spindle checkpoint regulator, regulates ciliogenesis in G0 phase (2011)
  • Author(s): Miyamoto, T., Kikuchi, A., Furutani-Seiki, M., Matsuura, S.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] The Dvl-associating protein Daple controls Rac activation and cell migration (2011)
  • Author(s): Ishida, M., Enomoto, A., Kikuchi, A., Takahashi, M.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Glypican-4の脂質ラフトへの局在に依存したWntシグナル伝達の制御機構 (2011)
  • Author(s): 坂根洋、山本英樹、松本真司、佐藤朗、菊池章
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] 翻訳後修飾によるWnt蛋白質の機能発現の制御 (2011)
  • Author(s): 山本英樹、粟田ちひろ、高尾敏文、岸田昭世、岸田想子、菊池章
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] Wntシグナルによる上皮形態形成制御とその異常による病態 (2011)
  • Author(s): 菊池章
  • Organizer: 第84回内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-22
• [Presentation] its signaling and implication in tumorigenesis (2011)
  • Author(s): Kikuchi, A.、Wnt5a
  • Organizer: 13th Japanese-German Cancer Workshop
  • Place of Presentation: Hiroshima
• [Book] 遺伝情報の発現制御-転写機構からエピジェネティクスまで- (2012)
  • Author(s): 菊池章(分担翻訳)
  • Total Pages: 30
  • Publisher: メディカル・サイエンス・インターナショナル
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/index.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/