Roles of the nectin-afadin system in epithelial-mesenchymal and mesenchymal-epithelial transitions

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790319
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kobe University
• Principal Investigator: OGITA Hisakazu Kobe University, 大学院・医学研究科, 准教授 (50379236)
• Project Period (FY): 2009 – 2010
• Keywords: ネクチン / アファディン / ネクチン様分子 / インテグリン / 増殖因子受容体 / 低分子量Gタンパク質 / がん

Research Abstract

The disruption of cell-cell junctions and the increase in cell movement play important roles in the epithelial-mesenchymal transition. On the other hand, the cell-cell junction formation and cell polarization at the interface between neighboring cells are crucial for the mesenchymal-epithelial transition. In this study, nectin-like molecules, which resemble cell adhesion molecules nectins in their molecular structure, afadin, which binds to the cytoplasmic region of nectins, and their related molecules were shown to promote the growth factor-induced cell movement. The underlying mechanisms were also elucidated. The interaction of afadin with another adaptor protein was essential for the cell polarization of epithelial cells.

Research Products

• [Journal Article] Role of afadin in vascular endothelial growth factor- and sphingosine 1-phosphate-induced angiogenesis. (2010)
  • Author(s): Tawa H, Rikitake Y, Takahashi M, Amano H, Miyata M, Satomi-Kobayashi S, Kinugasa M, Nagamatsu Y, Majima T, Ogita H, Miyoshi J, Hirata K, Takai Y.
  • Journal Title: Circ Res 106 Pages: 1731-1742
  • Peer Reviewed
• [Journal Article] Involvement of the Interaction of Afadin with ZO-1 in the Formation of Tight Junctions in Madin-Darby Canine Kidney Cells. (2010)
  • Author(s): Ooshio T, Kobayashi R, Ikeda W, Miyata M, Fukumoto Y, Matsuzawa N, Ogita H, Takai Y.
  • Journal Title: J Biol Chem 285 Pages: 5003-5012
  • Peer Reviewed
• [Journal Article] Cell adhesion molecules nectins and associating proteins : Implications for physiology and pathology. (2010)
  • Author(s): Ogita H, Rikitake Y, Miyoshi J, Takai Y.
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci 86 Pages: 621-629
  • Peer Reviewed
• [Journal Article] Overexpression of Necl-5 correlates with unfavorable prognosis in patients with lung adenocarcinoma. (2010)
  • Author(s): Nakai R, Maniwa Y, Tanaka Y, Nishio W, Yoshimura M, Okita Y, Ohbayashi C, Satoh N, Ogita H, Takai Y, Hayashi Y.
  • Journal Title: Cancer Sci 101 Pages: 1326-1330
  • Peer Reviewed
• [Journal Article] Regulation by Afadin of cyclical activation and inactivation of Rap1, Rac1, and RhoA Small G proteins at leading edges of moving NIH3T3 cells. (2009)
  • Author(s): Miyata M, Rikitake Y, Takahashi M, Nagamatsu Y, Yamauchi Y, Ogita H, Hirata KI, Takai Y.
  • Journal Title: J Biol Chem 284 Pages: 24595-24609
  • Peer Reviewed
• [Journal Article] Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor. (2009)
  • Author(s): Miyata M, Ogita H, Komura H, Nakata S, Okamoto R, Ozaki M, Majima T, Matsuzawa N, Kawano S, Minami A, Waseda M, Fujita N, Mizutani K, Rikitake Y, Takai Y.
  • Journal Title: J Cell Sci 122 Pages: 4319-4329
  • Peer Reviewed
• [Journal Article] Involvement of afadin in the formation and remodeling of synapses in the hippocampus. (2009)
  • Author(s): Majima T, Ogita H, Yamada T, Amano H, Togashi H, Sakisaka T, Tanaka-Okamoto M, Ishizaki H, Miyoshi J, Takai Y.
  • Journal Title: Biochem Biophys Res Commun 385 Pages: 539-544
  • Peer Reviewed
• [Journal Article] Silencing of ErbB3/ErbB2 signaling by immunoglobulin-like Necl-2. (2009)
  • Author(s): Kawano S, Ikeda W, Kishimoto M, Ogita H, Takai Y.
  • Journal Title: J Biol Chem 284 Pages: 23793-23805
  • Peer Reviewed
• [Presentation] 新しいがん浸潤・転移のメカニズム(がん研究入門コース) (2010)
  • Author(s): 扇田久和
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-23
• [Presentation] ネクチン?アファディン系による細胞の運動と接着制御におけるホスファターゼの役割と作用機構(シンポジウム) (2009)
  • Author(s): 扇田久和、高井義美
  • Organizer: 日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-10-23
• [Presentation] 接着分子と増殖因子受容体の相互作用とそのがん治療への応用に向けて(シンポジウム) (2009)
  • Author(s): 扇田久和、池田わたる、高井義美
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-02
• [Book] Nectins and Nectin-Like Molecules in the Nervous System. The Sticky Synapse (2009)
  • Author(s): Togashi H, Ogita H, Takai Y.
  • Total Pages: 185-206
  • Publisher: Springer
• [Remarks] ホームページ等
  • URL: http://www.med.kobe-u.ac.jp/mcb/index.html