The molecular mechanisms of the convergence in the early stage of the cell growth and adhesion signalings enhanced by glycosphingolipids

• Project/Area Number: 20590319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Chubu University
• Principal Investigator: FURUKAWA Keiko Chubu University, 生命健康科学部, 教授 (50260732)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 酸性スフィンゴ糖脂質 / GD3 / メラノーマ / インテグリン / 脂質ラフト / シグナル伝達 / ヒトメラノーマ細胞 / c-Met / HGF / Akt / 細胞膜脂質ラフト / I型コラーゲン / ILK / コラーゲンI / 細胞外マトリックス / p130Cas / paxillin

Research Abstract

Glycosphingolipid, GD3 is widely expressed in human malignant melanoma cells and tumors. In this study, we analyzed the molecular mechanisms for the convergence in the initial stage of the cell growth and adhesion signalings enhanced by GD3. Our results suggested that the signaling molecules were phosphorylated through the growth factor receptors more strongly in GD3-expressing cells than in GD3 negative cells. This was also the case for signaling via cell adhesion probably due to the assembly and clustering of integrins in lipid rafts, leading to the malignant properties of melanomas under GD3 expression.

Research Products

• [Journal Article] Functional activation of Src family kinase Yes is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3. (2011)
  • Author(s): Hamamura K., Tsuji M., Hotta H., Ohkawa Y., Takahashi M., Shibuya H., Nakashima H., Yamauchi Y., Hashimoto N., Hattori H., Ueda M., Furukawa K.
  • Journal Title: J.Biol.Chem. (in press)
  • Peer Reviewed
• [Journal Article] Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts : elucidation by a series of ganglioside-deficient mutant mice. (2011)
  • Author(s): Ohmi, Y.
  • Journal Title: J.Neurochem. Volume: 116 Pages: 926-35
  • Peer Reviewed
• [Journal Article] GM1/GD1b/GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft-localization of gangliosides in a melanoma cell line. (2010)
  • Author(s): Dong Y., Ikeda K., Hamamura K., Zhang Q., Kondo Y., Matsumoto Y., Ohmi Y., Furukawa K., Taguchi R.
  • Journal Title: Cancer Sci 101 Pages: 2039-2047
  • NAID: 10027831670
  • Peer Reviewed
• [Journal Article] Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains. (2010)
  • Author(s): Ohkawa Y., Miyazaki S., Hamamura H., Ohmi Y., Yamauchi Y., Furukawa K.
  • Journal Title: J.Biol.Chem. 285 Pages: 27213-27223
  • Peer Reviewed
• [Journal Article] Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains. (2010)
  • Author(s): Ohkawa, Y.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 27213-23
  • Peer Reviewed
• [Journal Article] GM1/GD1b/GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft-localization of gangliosides in a melanoma cell line. (2010)
  • Author(s): Dong, Y.
  • Journal Title: Cancer Sci. Volume: 101 Pages: 2039-47
  • Peer Reviewed
• [Journal Article] The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice. (2009)
  • Author(s): Greenshields K.N., Halstead S.K., Zitman F.M., Rinaldi S., Brennan K.M., O'Leary C., Chamberlain L.H., Easton A., Roxburgh J., Pediani J., Furukawa K., Goodyear C.S., Plomp J.J., Willison H.J.
  • Journal Title: J.Clin.Invest. 119 Pages: 595-610
  • Peer Reviewed
• [Journal Article] Glycoconjugate glycosyltransferases. (2009)
  • Author(s): Furukawa K., Tsuchida A., Okajima T.
  • Journal Title: Glycoconj. J. 26 Pages: 987-998
  • Peer Reviewed
• [Journal Article] Reduced motor and sensory functions and emotional response in GM3-only mice : emergence from early stage of life and exacerbation with aging. (2009)
  • Author(s): Tajima O., Egashira N., Ohmi Y., Fukue Y., Mishima M., Iwasaki K., Fujiwara M., Sugiura Y., Furukawa K.
  • Journal Title: Behav Brain Res. 198 Pages: 74-82
  • Peer Reviewed
• [Journal Article] Gangliosides play pivotal roles in the regulation of complement systems and in the maintenance of integrity in nerve tissues. (2009)
  • Author(s): Ohmi Y., Tajima O., Ohkawa Y., Mori A., Sugiura Y., Furukawa K.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 22405-22410
  • Peer Reviewed
• [Journal Article] Gangliosides play pivotal roles in the regulation of complement systems and in the maintenance of integrity in nerve tissues (2009)
  • Author(s): Ohmi, Y., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 22405-22410
  • Peer Reviewed
• [Journal Article] Immunologic glycosphingolipidomics and NKT cell development in mouse thymus (2009)
  • Author(s): Li, Y., et al.
  • Journal Title: Journal of Proteome Research 8 Pages: 2740-2751
  • Peer Reviewed
• [Journal Article] The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice (2009)
  • Author(s): Greenshields, K.N., et al.
  • Journal Title: J.Clin.Invest. 119 Pages: 595-610
  • Peer Reviewed
• [Journal Article] Essential roles of integrin-mediated signaling for the enhancement of malignant properties of melanomas based on the expression of GD3. (2008)
  • Author(s): Ohkawa Y., Miyazaki S., Miyata M., Hamamura K., Furukawa K.
  • Journal Title: Biochem.Biophys.Res.Commun. 373 Pages: 14-19
  • Peer Reviewed
• [Journal Article] Molecules in the signaling pathway activated by gangliosides can be targets of therapeutics for malignant melanomas. (2008)
  • Author(s): Furukawa K., Hamamura K., Nakashima H.
  • Journal Title: Proteomics 8 Pages: 3312-3316
  • Peer Reviewed
• [Journal Article] Disruption of GM2/GD2 synthase gene resulted in neo-expression of 9-O-acetyl GD3 irrespective of Tis21. (2008)
  • Author(s): Furukawa K., Aixinjueluo W., Kasama T., Ohkawa Y., Yoshihara M., Ohmi Y., Tajima O., Suzumura A., Kittaka D.
  • Journal Title: J.Neurochem. 105 Pages: 1057-1066
  • Peer Reviewed
• [Journal Article] Focal adhesion kinase as well as p130Cas and paxillin is crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. (2008)
  • Author(s): Hamamura K., Tsuji M., Nakashima H., Miyazaki S., Urano T., Yamamoto N., Ueda M., Furukawa K.
  • Journal Title: Biochim.Biophys.Acta 1780 Pages: 513-519
  • Peer Reviewed
• [Journal Article] Disruption of GM2/GD2 synthase gene resulted in neo-expressionof 9-O-acetyl GD3 irrespective of Tis21. (2008)
  • Author(s): Furukawa, K., Aixinjueluo, W., et al.
  • Journal Title: J. Neurochem. 105 Pages: 1057-1066
  • Peer Reviewed
• [Journal Article] Focal adhesion kinase as well as pl30Cas and paxillin is cruciallyinvolved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. (2008)
  • Author(s): Hamamura, K., Tsuji, M., et al.
  • Journal Title: Biochim. Biophys. Acta 1780 Pages: 513-519
  • Peer Reviewed
• [Journal Article] Essential roles of integrii'nediated signaling for the enhancementof malignant properties of melanomas based on the expression ofGD3. (2008)
  • Author(s): Ohkawa, Y., Miyazaki, S., et al.
  • Journal Title: Biochem Biophys Res Cotnmun. 373 Pages: 14-19
  • Peer Reviewed
• [Journal Article] Efficient generation of useful monoclonal antibodies reactive with globotriaosylceramide using knockout mice lacking Gb3/CD77 synthase.
  • Author(s): Kondo Y., Tokuda N., Furukawa K., Ando R., Uchikawa M., Zhang Q., Fan X., Furukawa K.
  • Journal Title: Glycoconj. J. (in press)
  • Peer Reviewed
• [Presentation] Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21. (2010)
  • Author(s): Furukawa K., Aixinjueluo W., T. Kasama Y. Ohkawa M. Yoshihara Y. Ohmi O. Tajima A. Suzumura D.Kittaka, K.Furukawa
  • Organizer: 4th ISN Special Neurochemistry Conference
  • Place of Presentation: Italy
• [Presentation] メラノーマ細胞のガングリオシドGD3による細胞増殖と接着シグナルの収斂と増強効果 (2010)
  • Author(s): 古川圭子、大川祐樹、神戸真理子、宮田麻衣子、章青、山森達也、高橋智絵、田島織絵、浜村和紀、古川鋼一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] メラノーマにおいてガングリオシドGD3はFAKの強い活性化を脂質ラフトで誘導する (2010)
  • Author(s): 大川裕樹、宮崎清香、神戸真理子、宮田麻衣子、橋本登、浜村和紀、古川圭子、古川鋼一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] ヒトメラノーマにおけるSrcファミリーキナーゼYesのガングリオシドGD3依存的活性化機構 (2010)
  • Author(s): 浜村和紀、辻桃子、堀田宏司、中島英行、橋本登、古川圭子、古川鋼一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] ヒト口腔扁平上皮癌におけるマーカーとしてのtype2HとLewisY抗原 (2010)
  • Author(s): 堀田公司、浜村和紀、豊國伸哉、渋谷英伸、徳田典代、古川圭子、山本憲幸、服部 宇、上田実、古川鋼一
  • Organizer: 第69回日本癌学会学術総
  • Place of Presentation: 大阪
• [Presentation] GM1合成酵素の発現はメラノーマ細胞株のガングリオシド修飾により腫瘍形成を抑制する (2010)
  • Author(s): 董宇、池田和貴、浜村和紀、章 青、近藤裕史、松本康之、大海雄介、山内祥生、古川圭子、田口良、古川鋼一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Disruption of GM2/GD2 synthase gene resulted in over expression of 9-O-acetyl GD3 irrespective of Tis21 (2010)
  • Author(s): Furukawa K., Aixinjueluo W., Kasama T., Ohmi Y., Ohkawa Y., Tajima O., Suzumura A., Kittaka.D.
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] Lysosomal accumulation of disease-associated gangliosides and small molecules that stimulate their lysosome-to-plasma membrane transport in Niemamm-Pick type C cells. (2010)
  • Author(s): Yamauchi Y., Yoshida K., Chang T., Furukawa K.
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] GM3 only miceの脊髄における神経変性機構の解明 (2010)
  • Author(s): 大海雄介、田島織絵、大川裕樹、古川圭子、古川鋼一
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] GM3 onlyマウスの中枢神経系におけるCCN5/Wisp2遺伝子の機能解析 (2010)
  • Author(s): 大川裕樹、大海雄介、田島織絵、稲垣邦江、徳田典代、古川圭子、古川鋼一
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] 糖鎖変異マウスにおける成長障害の分子メカニズム (2010)
  • Author(s): 田島織絵、藤田雄輝、大川裕樹、大海雄介、古川圭子、古川鋼一
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] Proteomic gangliosides-containing microdomains in malignant melanomas. (2010)
  • Author(s): Hashimoto N., Hamamura K., Ohmi Y., Ohkawa Y., Inagaki K., Furukawa K.
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] メラノーマ細胞のガングリオシドGD3による細胞増殖と接着シグナルの収斂と増強効果 (2010)
  • Author(s): 古川圭子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場・リーガロイヤル ホテル(大阪)
• [Presentation] スフィンゴ糖脂質による脂質ラフトの制御とその破綻 (2009)
  • Author(s): 古川鋼一、大海雄介、浜村和紀、古川圭子
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] Role of SREBP pathway in Akt signaling in human melanoma cells. (2009)
  • Author(s): Yamauchi Y., Furukawa K.
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 糖鎖欠損マウスにおける進行性神経機能障害の基盤としてのアセチルコリン受容体異常 (2009)
  • Author(s): 田島織絵、江頭伸昭、大海雄介、福江善彦、三島健一、岩崎克典、藤原道弘、杉浦康夫、古川圭子、古川鋼一
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] ヒトメラノーマの悪性形質におけるガングリオシドの役割 (2009)
  • Author(s): 大海雄介、大川祐樹、近藤裕史、橋本登、濱村和紀、古川圭子、古川鋼一
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] Adhesion of melanoma calls is enhanced by GD3 via recruitment of integrins to lipid rafts. (2009)
  • Author(s): Ohkawa Y., Miyazaki S., Hamamura K., Yamauchi Y., Furukawa K.
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
• [Presentation] ヒト口腔扁平上皮癌におけるtype 2HとLewis Y抗原の発現 (2009)
  • Author(s): 堀田宏司、浜村和紀、豊國伸哉、徳田典代、古川圭子、服部宇、上田実、古川鋼一
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] ヒトメラノーマにおける酸性糖脂質GD2の役割 (2009)
  • Author(s): 大海雄介、大川祐樹、近藤裕史、浜村和紀、古川圭子、古川鋼一
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] ヒトメラノーマ細胞における膜型シアリダーゼ(NEU3)の癌性形質への関与 (2009)
  • Author(s): 古川圭子、田島織絵、神戸真理子、宮田麻衣子、古川鋼一、宮城妙子
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] GM1/GD1b/GA1合成酵素発現によるSK-MEL-37メラノーマ細胞の腫瘍形質減弱の分子メカニズム (2009)
  • Author(s): 浜村和紀、董宇、池田和貴、章青、近藤裕史、松本康之、大海雄介、古川圭子、田口良、古川鋼一
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] GD3発現メラノーマ細胞においてインテグリンが脂質ラフトでクラスター構造を形成する (2009)
  • Author(s): 大川祐樹、宮崎清香、浜村和紀、宮田麻衣子、大海雄介、橋本登、田島織絵、古川圭子、古川鋼一
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] ヒトメラノーマ細胞においてSREBP経路はAktシグナルによって制御されている (2009)
  • Author(s): 山内祥生、古川圭子、古川鋼一
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] 細胞膜ミクロドメインの健常性維持と機能における酸性糖脂質の役割 (2009)
  • Author(s): 古川鋼一、大海雄介、田島織絵、大川祐樹、徳田典代、古川圭子
  • Organizer: 第29回日本糖質学会
  • Place of Presentation: 高山
• [Presentation] GM3 onlyマウスの神経変性における補体の役割 (2009)
  • Author(s): 大海雄介、田島織絵、大川祐樹、古川圭子、古川鋼一
  • Organizer: 第29回日本糖質学会
  • Place of Presentation: 高山
• [Presentation] ヒトメラノーマ細胞における膜型シアリダーゼ(NEU3)の癌性形質への関与 (2009)
  • Author(s): 古川圭子
  • Organizer: 第68回日本癌学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Molecular complex formation containing glycolipids for the regulation of signals. (2008)
  • Author(s): Furukawa K., Ohmi Y., Ohkawa Y., Kondo Y., Zhang Q., Furukwawa K.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] A small interfering RNA targeting adaptor molecules, p130Cas and paxillin as novel therapeutics for human melanomas. (2008)
  • Author(s): Makino Y., Hamamura K., Nakashima H., Furukawa K.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] Ganglioside GD3-dependent Akt signaling leads to activation of SREBP to regulate lipogenesis in melanoma cells. (2008)
  • Author(s): Yamauchi Y., Watanabe Y., Miyazaki S., Furukawa K.
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] 脂質ラフト構築におけるガングリオシドの役割 (2008)
  • Author(s): 大海雄介、田島織絵、大川裕樹、森 敦史、稲垣邦江、古川圭子、古川鋼一
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] ヒトメラノーマ細胞におけるシアリダーゼNeu3の癌性形質への関与 (2008)
  • Author(s): 古川圭子、田島織絵、神戸真理子、宮田麻衣子、宮城妙子、古川鋼一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 癌転移に関与する糖転移酵素の同定とその糖鎖産物の作用機構 (2008)
  • Author(s): 松本康之、章青、徳田典代、土田明子、古川圭子、浦野健、古川鋼一
  • Organizer: 第28回日本糖質学会
  • Place of Presentation: つくば
• [Presentation] ヒトメラノーマ細胞におけるシアリダーゼNeu3の癌性形質への関与。 (2008)
  • Author(s): 古川 圭子
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Book] 日本臨床(Drug discovery sciences in Japan with focus on molecular-targeted drugs 68) (2010)
  • Author(s): Furukawa K, Hamamura K, Ohkawa Y, Furukawa K.
  • Publisher: 日本臨床社
• [Book] 糖鎖生物学 第2版(監訳:鈴木康夫、木全弘治):14.シアル酸 (2010)
  • Author(s): 古川鋼一
  • Total Pages: 16
  • Publisher: コールドスプリングハーバー
• [Book] 蛋白質・核酸・酵素(Molecular complex in the vicinity of cell membrane generating cancer phenotypes 53) (2008)
  • Author(s): Furukawa K, Hamamura K, Ohkawa Y, Nakashima H, Zhang Q, Furukawa K.
  • Publisher: 共立出版
• [Book] 糖鎖情報の独自性と普遍性 蛋白質核酸酵素(2008年9月号増刊) : 癌細胞の形質を創出する細胞膜近傍の分子複合体 (2008)
  • Author(s): 古川 鋼一, その他
  • Publisher: 共立出版(東京)
• [Patent(Industrial Property Rights)] グロボ系糖脂質に対する効果的な抗体作成法 (2005)
  • Inventor(s): :古川鋼一、近藤裕史、安藤玲子、徳田典代、古川圭子
  • Industrial Property Rights Holder: 国立大学法人名古屋大学、株式会社GPバイオサイエンス
  • Filing Date: 2005-11-22