2003 Fiscal Year Annual Research Report

G蛋白共役型受容体による癌の浸潤・転移の制御とその分子メカニズム

Research Project

Project/Area Number	15024224
Research Institution	Kanazawa University
Principal Investigator	多久和陽金沢大学, 医学系研究科, 教授 (60171592)
Co-Investigator(Kenkyū-buntansha)	吉岡和晃金沢大学, 医学系研究科, 助手 (80333368) 多久和典子金沢大学, 医学系研究科, 助手 (70150290) 杉本直俊金沢大学, 医学系研究科, 講師 (80272954)
Keywords	癌 / 浸潤 / 転移 / G蛋白共役型受容体 / フィンゴシン-1-リン酸 / Rho / Rac / 遊走
Research Abstract	癌の浸潤・転移には、細胞運動はきわめて重要な役割を果たしていることは周知の事実である。新規脂質メディエータースフィンゴシン-1-リン酸(S1P)は、細胞膜表面G蛋白共役型受容体(GPCR)群Edgファミリーを介して、細胞遊走、形態変化などの多彩な生物活性を示す。特に、細胞運動に関しては、Edg1及びEdg3は細胞運動促進的に、Edg5は細胞運動抑制的に作用することをこれまでに明らかにして来た。本研究においてS1Pが内因性に発現しているEdg5受容体を介してマウスB16メラノーマ細胞のインビトロ浸潤を抑制すること、この作用にはRac活性の抑制とRho活性の促進が必要であること、さらに、尾静脈注入後肺転移モデルを用いてS1PがB16メラノーマ細胞の転移を抑制すること、この抑制作用もRac活性の抑制を介していると考えられることを示した。一方、Edg5とは正反対に、強制発現させたEdg1とEdg3は両者ともに浸潤・転移を促進し、この作用はRacの活性化を伴った。以上の結果から、Edg受容体はサブタイプ特異的にがん細胞の浸潤・転移を二方向性に制御しうること、さらにこれらの作用にはRac活性の二方向性制御が関与していることが示された。

Research Products

(9 results)

All Other

All Publications (9 results)

[Publications] Y.Banno et al.: "Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphatidylinositol 3-kinase or Akt, in chinese hamster ovary cells."Biochem.J.. 369. 363-368 (2003)
[Publications] H.Ikeda et al.: "Antiproliferative action of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5."Gastroenterology. 124. 459-469 (2003)
[Publications] N.Sugimoto et al.: "Inhibitory and stimulatory regulation of Rac and cell motility by the G_<12/13>-Rho-and the G_i-pathways integrated downstream of a single G protein coupled sphingosine-1-phosphate receptor isoform."Mol.Cell.Biol.. 23. 1534-1545 (2003)
[Publications] D.Shida et al.: "Lysophosphatidic acid enhances metastatic potential of human colon carcinoma DLD1 cells through LPA1."Cancer Res.. 63. 1706-1711 (2003)
[Publications] J.Xu et al.: "Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils."Cell.. 114. 201-214 (2003)
[Publications] K.Arikawa et al.: "Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor requirement of inhibition of cellular Rac activity."J.Biol.Chem.. 278. 32841-32851 (2003)
[Publications] H.Yamaguchi et al.: "Sphingosine-1-posphate receptor subtype-specific positive and negative regulation of Rac and hematogenous metastasis of melanoma cells."Biochem.J.. 374. 715-722 (2003)
[Publications] S.Usui et al.: "Blood lipid mediator sphingosine-1-phosphate potently stimulates platelet derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-denendent induction of kruppel-like factor 5."J.Biol.Chem.. (In press). (2004)
[Publications] M.Yamada et al.: "Overexpression of phospholopase, D prevents actinomycin D induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells."Biochem.J.. (In press). (2004)

2003 Fiscal Year Annual Research Report

G蛋白共役型受容体による癌の浸潤・転移の制御とその分子メカニズム

Principal Investigator

多久和 陽 金沢大学, 医学系研究科, 教授 (60171592)

Research Products

[Publications] Y.Banno et al.: "Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphatidylinositol 3-kinase or Akt, in chinese hamster ovary cells."Biochem.J.. 369. 363-368 (2003)

[Publications] H.Ikeda et al.: "Antiproliferative action of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5."Gastroenterology. 124. 459-469 (2003)

[Publications] N.Sugimoto et al.: "Inhibitory and stimulatory regulation of Rac and cell motility by the G_<12/13>-Rho-and the G_i-pathways integrated downstream of a single G protein coupled sphingosine-1-phosphate receptor isoform."Mol.Cell.Biol.. 23. 1534-1545 (2003)

[Publications] D.Shida et al.: "Lysophosphatidic acid enhances metastatic potential of human colon carcinoma DLD1 cells through LPA1."Cancer Res.. 63. 1706-1711 (2003)

[Publications] J.Xu et al.: "Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils."Cell.. 114. 201-214 (2003)

[Publications] K.Arikawa et al.: "Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor requirement of inhibition of cellular Rac activity."J.Biol.Chem.. 278. 32841-32851 (2003)

[Publications] H.Yamaguchi et al.: "Sphingosine-1-posphate receptor subtype-specific positive and negative regulation of Rac and hematogenous metastasis of melanoma cells."Biochem.J.. 374. 715-722 (2003)

[Publications] S.Usui et al.: "Blood lipid mediator sphingosine-1-phosphate potently stimulates platelet derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-denendent induction of kruppel-like factor 5."J.Biol.Chem.. (In press). (2004)

[Publications] M.Yamada et al.: "Overexpression of phospholopase, D prevents actinomycin D induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells."Biochem.J.. (In press). (2004)

多久和陽金沢大学, 医学系研究科, 教授 (60171592)