Role of cell adhesion signaling in the abnormal cell polarization of cancer cells

2009 Fiscal Year Final Research Report

• Project/Area Number: 17014055
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kobe University (2008-2009); Osaka University (2005-2007)
• Principal Investigator: TAKAI Yoshimi Kobe University, 大学院・医学研究科, 教授 (60093514)
• Co-Investigator(Kenkyū-buntansha): OGITA Hisakazu 神戸大学, 医学研究科, 准教授 (50379236) ; RIKITAKE Yoshiyuki 神戸大学, 医学研究科, 准教授 (50419488) ; TOGASHI Hideru 神戸大学, 医学研究科, 助教 (90415240) ; SAKISAKA Toshiaki 神戸大学, 医学研究科, 教授 (80359843) ; OKAMOTO Miki 大阪府立成人病センター, 分子生物学部門, 研究員 (20332455)
• Project Period (FY): 2005 – 2009
• Keywords: 細胞増殖 / 細胞運動 / 細胞接着 / 細胞極性 / ネクチン / Necl / インテグリン

Research Abstract

Cell adhesion molecules nectins and Necls were found to crucially regulate various cellular functions, including cell adhesion, polarization, morphology, movement, proliferation, differentiation, and survival, in cooperation with growth factor receptors and integrins. The molecular mechanisms underlying these functions were clearly elucidated. The dysfunctions of nectins and Necls were shown to be involved in the abnormal proliferation of cancer cells, leading to tumor invasion and metastasis. It was proposed that the normalization of the dysfunctions is the key to develop a new type of anti-cancer therapy.

Research Products

• [Journal Article] Involvement of the interaction of afadin with ZO-1 in the formation of tight junctions in MDCK 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] Laminin- based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5-α/(ss)□ (2010)
  • Author(s): Hotta A, Kawakatsu T, Nakatani T, Sato T, Matsui C, Sukezane T, Akagi T, Hamaji T, Grigoriev I, Akhmanova A, Takai Y, Mimori-Kiyosue Y.
  • Journal Title: J Cell Biol 189 Pages: 901-917
  • 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
• [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, K, Takai, Y.
  • Journal Title: J Biol Chem 284 Pages: 24595-24609
  • Peer Reviewed
• [Journal Article] Synaptic activity prompts γ-secretase- mediated cleavage of EphA4 and dendritic spine formation. (2009)
  • Author(s): Inoue E, Deguchi-Tawarada M, Togawa A, Matsui C, Arita K, Katahira-Tayama S, Sato T, Yamauchi E, Oda Y, Takai Y.
  • Journal Title: J Cell Biol 185 Pages: 551-564
  • 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] Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release. (2008)
  • Author(s): Sakisaka T, Yamamoto Y, Mochida S, Nakamura M, Nishikawa K, Ishizaki H, Okamoto-Tanaka M, Miyoshi J, Fujiyoshi Y, Manabe T, Takai, Y.
  • Journal Title: J Cell Biol 183 Pages: 323-337
  • Peer Reviewed
• [Journal Article] Involvement of nectin in inactivation of integrin αvss3 after the establishment of cell-cell adhesion. (2008)
  • Author(s): Sakamoto Y, Ogita H, Komura H, Takai Y.
  • Journal Title: J Biol Chem 283 Pages: 496-505
  • Peer Reviewed
• [Journal Article] Roles of Necl-5/Poliovirus receptor and ROCK in the regulation of transformation of integrin αv(ss)3-based focal complexes into focal adhesions. (2008)
  • Author(s): Nagamatsu Y, Rikitake Y, Takahashi M, Deki Y, Ikeda W, Hirata K, Takai Y.
  • Journal Title: J Biol Chem 283 Pages: 14532-14541
  • Peer Reviewed
• [Journal Article] Cross-talk among integrin, cadherin, and growth factor Receptor: roles of nectin and nectin-like molecule. (2008)
  • Author(s): Ogita H, Takai Y.
  • Journal Title: Int Rev Cytol 265 Pages: 1-54
  • Peer Reviewed
• [Journal Article] The immunoglobulin-like cell adhesion molecule nectin and its associated protein afadin. (2008)
  • Author(s): Takai Y, Ikeda W, Ogita H, Rikitake Y.
  • Journal Title: Annu Rev Cell Dev Biol 24 Pages: 309-342
  • Peer Reviewed
• [Journal Article] Nectins and nectin-like molecules : roles in contact inhibition of cell movement and proliferation. (2008)
  • Author(s): Takai Y, Miyoshi J, Ikeda W, Ogita H.
  • Journal Title: Nat Rev Mol Cell Biol 9 Pages: 603-615
  • Peer Reviewed
• [Journal Article] Up-regulation of loricrin expression by cell adhesion molecule nectin-1 through Rap1-ERK signaling in keratinocytes. (2007)
  • Author(s): Wakamatsu K, Ogita H, Okabe N, Irie K, Tanaka-Okamoto M, Ishizaki H, Ishida-Yamamoto A, Iizuka H, Miyoshi J, Takai, Y.
  • Journal Title: J Biol Chem 282 Pages: 18173-18181
  • Peer Reviewed
• [Journal Article] Necl-5/poliovirus receptor interacts in cis with integrin αvss3 and regulates its clustering and focal complex formation. (2007)
  • Author(s): Minami Y, Ikeda W, Kajita M, Fujito T, Amano H, Tamaru Y, Kuramitsu K, Sakamoto Y, Monden M, Takai, Y.
  • Journal Title: J Biol Chem 282 Pages: 18481-18496
  • Peer Reviewed
• [Journal Article] Regulation of platelet-derived growth factor receptor activation by afadin through SHP-2 : implications for cellular morphology. (2007)
  • Author(s): Nakata S, Fujita N, Kitagawa Y, Okamoto R, Ogita H, Takai Y.
  • Journal Title: J Biol Chem 282 Pages: 37815-37825
  • Peer Reviewed
• [Journal Article] Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. (2007)
  • Author(s): Hisata S, Sakisaka T, Baba T, Yamada T, Aoki K, Matsuda M, Takai Y.
  • Journal Title: J Cell Biol 178 Pages: 843-860
  • Peer Reviewed
• [Journal Article] Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions. (2007)
  • Author(s): Ooshio T, Fujita N, Yamada A, Sato T, Kitagawa Y, Okamoto R, Nakata S, Miki A, Irie K, Takai Y.
  • Journal Title: J Cell Sci 120 Pages: 2352-2365
  • Peer Reviewed
• [Journal Article] The roles of nectins in cell adhesions : cooperation with other cell adhesion molecules and growth factor receptors. (2007)
  • Author(s): Sakisaka T, Ikeda W, Ogita H, Fujita N, Takai Y.
  • Journal Title: Curr Opin Cell Biol 19 Pages: 593-602
  • Peer Reviewed
• [Journal Article] Regulation of the assembly and adhesion activity of E-cadherin by nectin and afadin for the formation of adherens junctions in Madin-Darby Canine Kidney Cells. (2006)
  • Author(s): Sato T, Fujita N, Yamada A, Ooshio T, Okamoto R, Irie K, Takai, Y.
  • Journal Title: J Biol Chem 281 Pages: 5288-5299
  • Peer Reviewed
• [Journal Article] Involvement of the Ras-Ras-activated Rab5 guanine nucleotide exchange factor RIN2-Rab5 pathway in the Hepatocyte Growth Factor-induced endocytosis of E-cadherin. (2006)
  • Author(s): Kimura T, Sakisaka T, Baba T, Yamada T, Takai Y.
  • Journal Title: J Biol Chem 281 Pages: 10598-10609
  • Peer Reviewed
• [Journal Article] Interaction of integrin αvss3 with nectin : Implication in cross-talk between cell-matrix and cell-cell junctions. (2006)
  • Author(s): Sakamoto Y, Ogita H, Hirota T, Kawakatsu T, Fukuyama T, Yasumi M, Kanzaki N, Ozaki M, Takai Y.
  • Journal Title: J Biol Chem 281 Pages: 19631-19644
  • Peer Reviewed
• [Journal Article] Activation of Rac by cadherin through the c-Src-Rap1- phosphatidylinositol 3-kinase-Vav2 pathway. (2006)
  • Author(s): Fukuyama T, Ogita H, Kawakatsu T, Inagaki M, Takai Y.
  • Journal Title: Oncogene 25 Pages: 8-19
  • Peer Reviewed
• [Journal Article] Requirement of nectin, but not cadherin, for formation of claudin- based tight junctions in annexin II- knockdown MDCK cells. (2006)
  • Author(s): Yamada A, Fujita N, Sato T, Okamoto R, Ooshio T, Hirota T, Morimoto K, Irie K, Takai Y.
  • Journal Title: Oncogene 25 Pages: 5085-5102
  • Peer Reviewed
• [Presentation] Nectins and nectin-like molecules: roles and modes of action in tumorigenesis, nvasion, and metastasis. (2009)
  • Author(s): 高井義美
  • Organizer: Global COE Inter- national Symposium "New Aspects in Immunology and Cancer Research"
  • Place of Presentation: Akita, Japan
  • Year and Date: 20090600
• [Presentation] 細胞接着とシグナル伝達-生理機能と病態 (2008)
  • Author(s): 高井義美
  • Organizer: 第31回日本血栓止血 学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20081100
• [Presentation] がん化による細胞接着・運動・増殖異常とその分子機構 (2008)
  • Author(s): 扇田久和、高井義美
  • Organizer: 第67回日本癌学会総会(シンポジウム)
  • Place of Presentation: 名古屋
  • Year and Date: 20081000
• [Presentation] 細胞の極性形成の基本メカニズム (2008)
  • Author(s): 高井義美
  • Organizer: 第8回日本分子生物学会春季シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 20080500
• [Presentation] Roles and modes of action of nectin and nectin-like molecule in cell polarization. (2007)
  • Author(s): 高井義美
  • Organizer: International Symposium on Cell Polarity System and Future Medicine "Revealing the Mechanism of Cell Morphogenesis for Future Medicine"
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20071200
• [Presentation] Cell-cell adhesion and formation of cell polarity (2007)
  • Author(s): 高井義美
  • Organizer: 第66回日本癌学会学術総会(シンポジウム)
  • Place of Presentation: 横浜
  • Year and Date: 20071000
• [Presentation] Cell adhesion and signal Transduction. (2007)
  • Author(s): 高井義美
  • Organizer: Mini-symposium to celebrate 30th anniversary of Institute of Biological Chemistry (IBC) "Proteins from chemistry to biology"
  • Place of Presentation: Taiwan
  • Year and Date: 20071000
• [Presentation] Roles of nectin and nectin-like molecule in contact inhibition of cell movement. (2007)
  • Author(s): 高井義美
  • Organizer: 6th Abercrombie Meeting on Cell Migration : from molecules to organisms
  • Place of Presentation: Oxford, UK
  • Year and Date: 20070900
• [Presentation] Cross-talk between cell-cell and cell-matrix junctions through nectin and nectin-like molecule. (2007)
  • Author(s): 高井義美
  • Organizer: Gordon Research Conferences "Cell Contact & Adhesion"
  • Place of Presentation: Lucca, Italy
  • Year and Date: 20070500-20070600
• [Presentation] 細胞の接着とシグナリング機構 (2007)
  • Author(s): 高井義美
  • Organizer: 日本生化学会東北支部第73回例会(シンポジウム)
  • Place of Presentation: 仙台
  • Year and Date: 20070500
• [Presentation] 細胞間接着による細胞の運動・増殖機構 (2007)
  • Author(s): 高井義美
  • Organizer: 第39回日本結合組織学会・第54回日本マトリックス研究会合同学術集会
  • Place of Presentation: 東京
  • Year and Date: 20070500
• [Presentation] Cell adhesion and signal transduction (2007)
  • Author(s): 高井義美
  • Organizer: 第71回日本循環器学会総会(真下記念講演)
  • Place of Presentation: 神戸
  • Year and Date: 20070300
• [Presentation] がん細胞の異常増殖と浸潤・転移の分子機構 (2006)
  • Author(s): 高井義美
  • Organizer: 第65回日本癌学会学術総会(モーニングレクチャー)
  • Place of Presentation: 横浜
  • Year and Date: 20060900
• [Presentation] Nectin and nectin-like molecules in cell adhesion, movement, and proliferation. (2006)
  • Author(s): 高井義美
  • Organizer: The 55th Fujihara International Seminar "Physiological and pathological significance of the cell to cell interaction by TSLC1/1GSF4"
  • Place of Presentation: Hokkaido, Japan
  • Year and Date: 20060700
• [Presentation] Regulation of cell polarization, movement, and proliferation by cell-cell adhesion molecule nectin. (2006)
  • Author(s): 高井義美, 藤田直之, 扇田久和, 池田わたる
  • Organizer: 20^<th> IUBMB International Congress of Biochemistry and Molecular Biology and 11^<th> FAOBMB Congress
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20060600
• [Presentation] 月田先生から学んだ私の細胞接着研究 (2006)
  • Author(s): 高井義美
  • Organizer: 第3次対がん10か年総合戦略(平成16年度-25年度)第1回合同シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20060200
• [Presentation] New cross-talk mechanisms of cell adhesion, migration and proliferation. (2006)
  • Author(s): 高井義美, 池田わたる, 扇田久和, 匂坂敏朗, 藤田直之
  • Organizer: The 10th International Symposium on Cancer Chemotherapy "Growth Signal, Drug Resistance and Metastasis in the Development of Molecular Cancer Therapeutics"
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20060100
• [Presentation] Cross-talk signaling between cell adhesion and cell movement and proliferation (2005)
  • Author(s): 高井義美、池田わたる、扇田久和、匂坂敏朗、藤田直之
  • Organizer: 第78回日本生化学会大会(シンポジウム)
  • Place of Presentation: 神戸
  • Year and Date: 20051000
• [Presentation] がん細胞の接着と極性の異常 (2005)
  • Author(s): 高井義美
  • Organizer: 第64回日本癌学会学術総会(モーニングレクチャー)
  • Place of Presentation: 札幌
  • Year and Date: 20050900
• [Presentation] Temporal and spatial control of intracellular signaling. (2005)
  • Author(s): 高井義美
  • Organizer: Inter- national Symposium on Leading Project for Biosimulation
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20050700
• [Presentation] がん細胞の浸潤・転移の新しい分子機構 (2005)
  • Author(s): 高井義美
  • Organizer: 第14回日本がん転移学会総会(特別講演)
  • Place of Presentation: 大阪
  • Year and Date: 20050600
• [Presentation] Signaling by nectins and nectin-like molecules in cell adhesion, migration and proliferation. (2005)
  • Author(s): 高井義美
  • Organizer: Gordon Research Conferences "Mechanisms of Cell Signalling"
  • Place of Presentation: Hong Kong
  • Year and Date: 20050600
• [Book] A cell-free assay for endocytosis of E-cadherin.(In Methods in Molecular Biology)(Vol.440) (2007)
  • Author(s): Sakisaka T, Takai Y.
  • Total Pages: 77-87
  • Publisher: Humana Press, Totowa
• [Book] Activation of Rap1, Cdc42, and Rac by nectin adhesion system.(In Methods Enzymol)(Vol.406) (2006)
  • Author(s): Ogita H, Takai Y.
  • Total Pages: 415-424
  • Publisher: Academic Press, San Diego
• [Book] Nectins and nectin- like molecules : Roles in cell adhesion, polarization, movement, and proliferation.(In IUBMB Life)(Vol.58) (2006)
  • Author(s): Ogita H, Takai, Y.
  • Total Pages: 334-343
  • Publisher: Taylor & Francis, Oxford
• [Book] Purification and properties of Rab3 GEP (DENN/MADD).(In Methods Enzymol)(Vol.403) (2005)
  • Author(s): Sakisaka T, Takai, Y.
  • Total Pages: 254-261
  • Publisher: Academic Press, San Diego
• [Book] Purification and properties of Rabconnectin-3.(In Methods Enzymol)(Vol.403) (2005)
  • Author(s): Sakisaka T, Takai, Y.
  • Total Pages: 401-407
  • Publisher: Academic Press, San Diego
• [Book] Molecular perspective on tight-junction assembly and epithelial polarity.(In Advanced Drug Delivery Rev)(Vol.57) (2005)
  • Author(s): Miyoshi J, Takai Y.
  • Total Pages: 815-855
  • Publisher: Elsevier Science, Amsterdam
• [Remarks] ホームページ等
  • URL: http://www.med.kobe-u.ac.jp/mcb/index.html