Molecular pathological analyses of Wnt5a-Ror signaling in inflammation and cancer progression accompanying epithelial-mesenchymal transition

• Project/Area Number: 24390080
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kobe University
• Principal Investigator: MINAMI Yasuhiro 神戸大学, 医学(系)研究科(研究院), 教授 (70229772)
• Co-Investigator(Kenkyū-buntansha): NISHITA Michiru 神戸大学, 大学院医学研究科, 准教授 (30379359) ; ENDO Mitsuharu 神戸大学, 大学院医学研究科, 助教 (90436444)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: Wnt5a-Ror / シグナル伝達 / 上皮間葉転換 (EMT) / 慢性炎症 / がんの増悪 / 組織損傷修復 / 炎症性サイトカイン / Wnt5a-Rorシグナル / 上皮間葉転換 / 炎症 / がんの進展・増悪 / 遺伝子発現制御 / 癌

Outline of Final Research Achievements

Wnt5a-Ror signaling has been shown to be activated transiently during embryogenesis and to play important roles in developmental morphogenesis and tissue-genesis via induction of epithelial-mesenchymal transition and so on. After birth, expression levels of Wnt5a and Ror proteins are very low in general. In this study, we have shown by employing in vitro and in vivo analyses that these proteins are induced during tissue repair after injury, chronic inflammation, and progression of cancers, thereby resulting in aberrant activation of Wnt5a-Ror signaling. We have also found possible relationships between these pathological conditions and aberrant activation of Wnt5a-Ror signaling.

Research Products

• [Journal Article] Insight into the role of Wnt5a-induced signaling in normal and cancer cells. (2015)
  • Author(s): Endo, M., Nishita, M., Fujii, M., Minami, Y.
  • Journal Title: Int. Rev. Cell Mol. Biol. Volume: 314 Pages: 117-148
  • DOI: 10.1016/bs.ircmb.2014.10.003
  • ISBN: 9780128022832
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-g 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. Report Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Diabetic osteopenia by decreased β-catenin signaling is partly induced by epigenetic derepression of sFRP-4 gene (2014)
  • Author(s): Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, Minami Y, Haraguchi R, Takahashi Y, Kitazawa S.
  • Journal Title: PLoS One Volume: 9 Issue: 7 Pages: e102797-e102797
  • DOI: 10.1371/journal.pone.0102797
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of Wnt5a-Ror2 signaling in morphogenesis of the metanephric mesenchyme during ureteric budding (2014)
  • Author(s): Nishita M, Qiao S, Miyamoto M, Okinaka Y, Yamada M, Hashimoto R, Iijima K, Otani H, Hartmann C, Nishinakamura R, Minami Y
  • Journal Title: Mol Cell Biol Volume: 34 Issue: 16 Pages: 3096-3105
  • DOI: 10.1128/mcb.00491-14
  • Peer Reviewed / Open Access
• [Journal Article] Critical role of Frizzledl in age-related alterations of Wnt/β-catenin signal in myogenic cells during differentiation. (2014)
  • Author(s): Doi R, Endo M, Yamakoshi K, Y amanashi Y, Nishita M, Fukada SI. Minami Y.
  • Journal Title: Genes Cells. Volume: 19 Issue: 4 Pages: 287-296
  • DOI: 10.1111/gtc.12132
  • Peer Reviewed / Open Access
• [Journal Article] IL-6-accelerated calcification by induction of Ror2 in human adipose tissue-derived mesenchymal stem cells is STAT3-dependent. (2014)
  • Author(s): Fukuyo, S., Yamaoka, K., Sonomoto, K., Oshita, K., Okada, Y., Saito, K., Yoshida, Y., Kanazawa, T., Minami, Y., Tanaka, Y.
  • Journal Title: Rheumatology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Noncanonical Wnt5a enhances Wnt/-catenin signaling during osteogenesis. (2014)
  • Author(s): Okamoto, M., Udagawa, N., Yamashita, T., Nakamichi, Y., Uehara, S., Kato, H., Saito, N., Minami, Y., Takahashi, N., Kobayashi, Y.
  • Journal Title: Sci. report Volume: 4 Issue: 1 Pages: 4493-4493
  • DOI: 10.1038/srep04493
  • Peer Reviewed / Open Access
• [Journal Article] Activation of Wnt5a-Ror2 signaling associated with epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells during renal fibrosis. (2013)
  • Author(s): Li, X., Yamagata, K., Nishita, M., Endo, M., Arfian, N., Rikitake, Y., Emoto, N., Hirata, K., Tanaka, Y., Minami, Y.
  • Journal Title: Genes Cells Volume: 18 Issue: 7 Pages: 608-619
  • DOI: 10.1111/gtc.12064
  • Peer Reviewed
• [Journal Article] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2012)
  • Author(s): Endo M, Doi R, Nishita M, Minami Y
  • Journal Title: Journal of Cell Science Volume: (印刷中)(掲載確定) Pages: 2017-2029
  • DOI: 10.1242/jcs.097782
  • Peer Reviewed
• [Journal Article] 非古典的Wntシグナルによる極性と幹細胞性維持の制御 (2012)
  • Author(s): 遠藤光晴、南康博
  • Journal Title: 生体の科学(特集 : 細胞極性の制御) Volume: 63 Pages: 224-228
• [Presentation] Role of NF-κB-mediated expression of Ror1 during skeletal muscle regeneration (2014)
  • Author(s): Koki Kamisaki, Ryosuke Doi, Suguru Kato, Soichiro Fukada, Motoi Kanagawa, Tatsushi, Mitsuharu Endo, Yasushiro Minami
  • Organizer: UNIVERSITY OF WASHINGTON-KOBE UNIVERSITY INTERNATIONAL SYMPOSIUM ON MEMBRANE BIOLOGY
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2014-12-15
• [Presentation] 受容体型チロシンキナーゼRor1による骨格筋再生制御 (2014)
  • Author(s): 加藤 英、土井 亮助、遠藤 光晴、深田 宗一郎、金川 基、戸田 達史、南 康博
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-27
• [Presentation] Role of Wnt5a-Ror2 signaling in patterning the metanephric mesenchyme during ureteric budding (2014)
  • Author(s): Michiru Nishita, Sen Qiao, Mari Miyamoto, Yuka Okinaka, Makiko Yamada, Ryuju Hashimoto, Kazumoto Iijima, Hiroki Otani, Christine Hartmann, Ryuichi Nishinakamura, Yasuhiro Minami
  • Organizer: Keystone Symposia "Developmental Pathways and Cancer: Wnt, Notch and Hedgehog(J7)"
  • Place of Presentation: Banff, Canada
• [Presentation] Roles of Wnt5a-Ror Signaling in Pathological Conditions (2014)
  • Author(s): Yasuhiro Minami
  • Organizer: UNIVERSITY OF WASHINGTON-KOBE UNIVERSITY SYMPOSIUM ON MEMBRANE BIOLOGY
  • Place of Presentation: UW, Seattle, U.S.A.
  • Invited
• [Presentation] 筋損傷・再生過程における受容体型チロシンキナーゼRor1の発現解析 (2013)
  • Author(s): 土井 亮助、遠藤 光晴、南 康博
  • Organizer: 第60回日本生化学会近畿支部例会
  • Place of Presentation: 大阪
• [Presentation] Roles of Wnt/PCP signaling in pathological conditions of epithelial tubular tissues (2013)
  • Author(s): Yasuhiro Minami, Kaoru Yamagata, Mitsuharu Endo, Hiroki Otani, Ryuichi Nishinakamura, Michiru Nishita
  • Organizer: First International Meeting for Epithelial Tubulology
  • Place of Presentation: 札幌
  • Invited
• [Presentation] 炎症性サイトカインによりアストロサイトで発現誘導されるRor1受容体の機能解析 (2013)
  • Author(s): 遠藤 光晴、土井 亮助、西田 満、南 康博
  • Organizer: 2013年度包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋
• [Presentation] 尿管芽形成におけるWnt5a-Ror2シグナルの役割と腎尿路奇形 (2013)
  • Author(s): 西田 満, 喬 森,宮本 真里, 沖中 由佳, 山田 真紀子, 飯島 一誠, 大谷 浩, Christine Hartmann, 西中村 隆一, 南 康博
  • Organizer: 第22回発達腎研究会
  • Place of Presentation: 大阪（高槻）
  • Invited
• [Presentation] Functional analysis of Wnt5a-Ror signaling in regulation of progenitor proliferation during neocortical neurogenesis (2013)
  • Author(s): Mtisuharu Endo, Yasuhiro Minami
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] 反応性アストロサイトにおけるRorファミリー受容体型チロシンキナーゼの役割 (2013)
  • Author(s): 遠藤 光晴、加藤 英、疋田 壮舞、南 康博
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 骨格筋分化・再生モデルを用いたRorシグナルの機能解析 (2012)
  • Author(s): 土井亮介、遠藤光晴、南康博
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ
  • Year and Date: 2012-12-14
• [Presentation] マウス腎臓発生におけるWnt5a-Ror2シグナルの役割 (2012)
  • Author(s): 西田満、喬森、宮本真理、山田真紀子、大谷浩、Christine Hartmann、西中村隆一、南康博
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ
  • Year and Date: 2012-12-14
• [Book] ROR Receptor Tyrosine Kinase Family (Chapter 13) Receptor Tyrosine Kinases: Family and subfamilies (2015)
  • Author(s): Endo, M., Nishita, M., Doi, R., Hayashi, M., Minami, Y.
  • Publisher: Springer Science
• [Book] The Receptor Tyrosine Kinase Handbook (2014)
  • Author(s): Endo, M., Nishita, M., Doi, R., Minami, Y. (Wheeler, D. L., Yarden, Y. edited)
  • Publisher: Springer Science
• [Book] Progenitor Cells: Biology, Characterization and Potential Clinical Applications (2013)
  • Author(s): Endo, M., Minami, Y. (Horton, P. M., Lawrence, B. E. edited)
  • Total Pages: 16
  • Publisher: Nova Science Publishers, Inc.
• [Book] The Receptor Tyrosine Kinase Handbook (chapter : Ror receptor family) (2013)
  • Author(s): Endo, M., Nishita, M., Doi, R., Minami, Y.
  • Publisher: Springer Science(印刷中) (掲載確定)
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