Regulation by Nectin-like molecules of hemidesmosome disassembly and reorganization

• Project/Area Number: 24790284
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: MIZUTANI Kiyohito 神戸大学, 医学(系)研究科(研究院), 講師 (50559177)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ヘミデスモソーム / インテグリン / Necl / Necl-4 / CADM4 / ErbB3 / PTPN13 / 血管内皮細胞

Outline of Final Research Achievements

Hemidesmosomes are one of the cell-extracellular matrix junctions. However, the molecular mechanisms that regulate disassembly and reorganization of hemidesmosomes still remain unclear. In this study, we found that 1) Necl-4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly and 2) Necl-4 serves as a regulator for contact inhibition of cell movement and proliferation cooperatively with the VEGF receptor and PTPN13.

Research Products

• [Journal Article] The cell adhesion molecule necl-4/cadm4 serves as a nobel regulator for contact inhibition of cell movement and proliferation. (2015)
  • Author(s): Yamana S, Tokiyama A, Mizutani K, Hirata K, Takai Y, Rikitake Y.
  • Journal Title: PloS One. Volume: 10 Issue: 4 Pages: e0124259-e0124259
  • DOI: 10.1371/journal.pone.0124259
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of the TGF-β1-induced protein expression of SNAI1 and N-cadherin by miR-199a. (2014)
  • Author(s): Suzuki T, Mizutani K, Minami A, Nobutani K, Kurita S, Nagino M, Shimono Y, Takai Y.
  • Journal Title: Genes Cells. Volume: 19 Issue: 9 Pages: 667-675
  • DOI: 10.1111/gtc.12166
  • Peer Reviewed / Open Access
• [Journal Article] Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium. (2014)
  • Author(s): Tanaka-Okamoto M, Itoh Y, Miyoshi J, Mizoguchi A, Mizutani K, Takai Y, Inoue M.
  • Journal Title: PLoS One. Volume: 9 Issue: 10 Pages: e110549-e110549
  • DOI: 10.1371/journal.pone.0110549
  • Peer Reviewed / Open Access
• [Journal Article] Absence of primary cilia in cell cycle-arrested human breast cancer cells. (2014)
  • Author(s): Nobutani K, Shimono Y, Yoshida M, Mizutani K, Minami A, Kono S, Mukohara T, Yamasaki T, Itoh T, Takao S, Minami H, Azuma T, Takai Y.
  • Journal Title: Genes Cells. Volume: 19 Issue: 2 Pages: 141-152
  • DOI: 10.1111/gtc.12122
  • Peer Reviewed
• [Journal Article] Reduction of the ST6 β-galactosamide α-2,6-sialyltransferase 1 (ST6GAL1)-catalyzed sialylation of nectin-like molecule 2/cell adhesion molecule 1 and enhancement of ErbB2/ErbB3 signaling by microRNA-199a. (2013)
  • Author(s): Minami A, Shimono Y, Mizutani K, Nobutani K, Momose K, Azuma T, Takai Y.
  • Journal Title: J Biol Chem. Volume: 288 Issue: 17 Pages: 11845-11853
  • DOI: 10.1074/jbc.m112.405993
  • NAID: 40019873148
  • Peer Reviewed / Open Access
• [Journal Article] Interaction of Necl-4/CADM4 with ErbB3 and integrin α6 β4 and inhibition of ErbB2/ErbB3 signaling and hemidesmosome disassembly. (2013)
  • Author(s): Sugiyama H, Mizutani K, Kurita S, Okimoto N, Shimono Y, Takai Y.
  • Journal Title: Genes Cells. Volume: 18 Issue: 6 Pages: 519-528
  • DOI: 10.1111/gtc.12056
  • Peer Reviewed / Open Access
• [Journal Article] miR-214 and hypoxia down-regulate Necl-2/CADM1 and enhance ErbB2/ErbB3 signaling. (2013)
  • Author(s): Momose, K.
  • Journal Title: Genes Cells Volume: 18 Issue: 3 Pages: 195-202
  • DOI: 10.1111/gtc.12027
  • Peer Reviewed
• [Presentation] マイクロRNA-199aはTGFβ1で誘導されるSNAI1とN-cadherinの発現を抑制する (2014)
  • Author(s): 鈴木俊裕、水谷清人、南晶洋、信谷健太郎、梛野正人、下野洋平、高井義美
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] マイクロRNA-199aによるネクチン様分子２のシアル化修飾の減少とErbB2/ErbB3シグナル伝達の増強 (2013)
  • Author(s): 下野洋平、南晶洋、水谷清人、信谷健太郎、百瀬健次、東健、高井義美
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ヒト正常乳腺と乳がん組織における細胞接着分子ネクチン、アファディン、およびネクチン様分子 (2013)
  • Author(s): 北山美登里、下野洋平、信谷健太郎、水谷清人、向原徹、南博信、古森孝英、高井義美
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 大腸がん細胞においてマイクロRNA-214はNecl-2を抑制しErbB2/ErbB3シグナル伝達路を活性化する (2012)
  • Author(s): 百瀬健次、下野洋平、南晶洋、信谷健太郎、水谷清人、東健、高井義美
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Remarks] 神戸大学大学院 医学研究科 生化学・分子生物学講座 シグナル統合学分野 病態シグナル学部門
  • URL: http://www.med.kobe-u.ac.jp/ps/index.html
• [Remarks] 病態シグナル学ウェブサイト
  • URL: http://www.med.kobe-u.ac.jp/ps/index.html
• [Remarks] http://www.med.kobe-u.ac.jp/mcb/index.html