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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳建春 | |
| dc.contributor.author | Yun-Ju Huang | en |
| dc.contributor.author | 黃韻如 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:56:40Z | - |
| dc.date.available | 2008-08-13 | |
| dc.date.copyright | 2008-08-13 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-06-10 | |
| dc.identifier.citation | 1. Alemà S, Salvatore AM. p120 catenin and phosphorylation: Mechanisms and traits of an unresolved issue. Biochim Biophys Acta. 2007;1773:47-58.
2. An S, Bleu T, Hallmark OG, Goetzl EJ. Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J Biol Chem. 1998;273:7906-10. 3. Anastasiadis PZ, Moon SY, Thoreson MA, Mariner DJ, Crawford HC, Zheng Y, Reynolds AB. Inhibition of RhoA by p120 catenin. Nat Cell Biol 2000;2:637-44. 4. Andreev J, Galisteo ML, Kranenburg O, Logan SK, Chiu ES, Okigaki M, Cary LA, Moolenaar WH, Schlessinger J. Src and Pyk2 mediate G-protein-coupled receptor activation of epidermal growth factor receptor (EGFR) but are not required for coupling to the mitogen-activated protein (MAP) kinase signaling cascade. J Biol Chem. 2001;276:20130-5. 5. Angelini DJ, Hyun SW, Grigoryev DN, Garg P, Gong P, Singh IS, Passaniti A, Hasday JD, Goldblum SE. TNF-alpha increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia. Am J Physiol Lung Cell Mol Physiol. 2006;291:L1232-45. 6. Balsamo J, Arregui C, Leung T, Lilien J. The nonreceptor protein tyrosine phosphatase PTP1B binds to the cytoplasmic domain of N-cadherin and regulates the cadherin-actin linkage. J Cell Biol. 1998;143:523-32. 7. Bian D, Su S, Mahanivong C, Cheng RK, Han Q, Pan ZK, Sun P, Huang S. Lysophosphatidic Acid Stimulates Ovarian Cancer Cell Migration via a Ras-MEK Kinase 1 Pathway. Cancer Res 2004;64:4209-17. 8. Bian D, Mahanivong C, Yu J, Frisch SM, Pan ZK, Ye RD, Huang S. The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migration. Oncogene 2006;25:2234-44. 9. Biscardi JS, Belsches AP, Parsons SJ. Characterization of human epidermal growth factor receptor and c-Src interactions in human breast tumor cells. Mol Carcinog. 1998;2:261-72. 10. Boguslavsky S, Grosheva I, Landau E, Shtutman M, Cohen M, Arnold K, Feinstein E, Geiger B, Bershadsky A. p120 catenin regulates lamellipodial dynamics and cell adhesion in cooperation with cortactin. Proc Natl Acad Sci U S A. 2007;104:10882-7. 11. Brady-Kalnay SM, Mourton T, Nixon JP, Pietz GE, Kinch M, Chen H, Brackenbury R, Rimm DL, Del Vecchio RL, Tonks NK. Dynamic interaction of PTPmu with multiple cadherins in vivo. J Cell Biol. 1998;141:287-96. 12. Burks J, Agazie YM. Modulation of alpha-catenin Tyr phosphorylation by SHP2 positively effects cell transformation induced by the constitutively active FGFR3. Oncogene. 2006;25:7166-79. 13. Calautti E, Cabodi S, Stein PL, Hatzfeld M, Kedersha N, Paolo Dotto G. Tyrosine phosphorylation and src family kinases control keratinocyte cell-cell adhesion. J Cell Biol 1998;141:1449-65. 14. Castano J, Solanas G, Casagolda D, Raurell I, Villagrasa P, Bustelo XR, Garcia de Herreros A, Dunach M. Specific phosphorylation of p120-catenin regulatory domain differently modulates its binding to RhoA. Mol Cell Biol 2007;27:1745-57. 15. Chap H, Mauco G, Perret B, Simon MF, Douste-Blazy L. Role of exogenous phospholipases in triggering platelet aggregation. Adv Prostaglandin Thromboxane Res 1978;3:97-104. 16. Chou CH, Wei LH, Kuo ML, Huang YJ, Lai KP, Chen CA, Hsieh CY. Up-regulation of interleukin-6 in human ovarian cancer cell via a Gi/PI3K-Akt/NF-kappaB pathway by lysophosphatidic acid, an ovarian cancer-activating factor. Carcinogenesis 2005;26:45-52. 17. Daniel JM, Reynolds AB. Tyrosine phosphorylation and cadherin/catenin function. Bioessays. 1997;19:883-91. 18. Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature. 1996;379:557-60. 19. Daub H, Wallasch C, Lankenau A, Herrlich A, Ullrich A. Signal characteristics of G protein-transactivated EGF receptor. Embo J 1997;16:7032-44. 20. Davis MA, Ireton RC, Reynolds AB. A core function for p120-catenin in cadherin turnover. J Cell Biol 2003;163:525-34. 21. Dikic I, Tokiwa G, Lev S, Courtneidge SA, Schlessinger J. A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation. Nature 1996;383:547-50. 22. Do TV, Symowicz JC, Berman DM, Liotta LA, Petricoin EF 3rd, Stack MS, Fishman DA. Lysophosphatidic acid down-regulates stress fibers and up-regulates pro-matrix metalloproteinase-2 activation in ovarian cancer cells. Mol Cancer Res. 2007;5:121-31. 23. Downing JR, Reynolds AB. PDGF, CSF-1, and EGF induce tyrosine phosphorylation of p120, a pp60src transformation-associated substrate. Oncogene. 1991;6:607-13. 24. Eichholtz T, Jalink K, Fahrenfort I, Moolenaar WH. The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J. 1993;291:677-80. 25. Fang X, Schummer M, Mao M, Yu S, Tabassam FH, Swaby R, Hasegawa Y, Tanyi JL, LaPushin R, Eder A, Jaffe R, Erickson J, et al. Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim Biophys Acta 2002;1582:257-64. 26. Fishman DA, Liu Y, Ellerbroek SM, Stack MS. Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res 2001;61:3194-9. 27. Fourcade O, Simon MF, Viodé C, Rugani N, Leballe F, Ragab A, Fournié B, Sarda L, Chap H. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell. 1995;80:919-27. 28. Furui T, LaPushin R, Mao M, Khan H, Watt SR, Watt MA, Lu Y, Fang X, Tsutsui S, Siddik ZH, Bast RC, Mills GB. Overexpression of edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner. Clin Cancer Res 1999;5:4308-18. 29. Goetzl EJ, Dolezalova H, Kong Y, Hu YL, Jaffe RB, Kalli KR, Conover CA. Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res 1999;59:5370-5. 30. Gschwind A, Zwick E, Prenzel N, Leserer M, Ullrich A. Cell communication networks: epidermal growth factor receptor transactivation as the paradigm for interreceptor signal transmission. Oncogene. 2001;20:1594-600 31. Gumbiner BM. Regulation of cadherin adhesive activity. J Cell Biol. 2000;148:399-404. 32. Haskell MD, Slack JK, Parsons JT, Parsons SJ. c-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes. Chem Rev. 2001;101:2425-40. 33. Hu YL, Tee MK, Goetzl EJ, Auersperg N, Mills GB, Ferrara N, Jaffe RB. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst 2001;93:762-8. 34. Hu YL, Albanese C, Pestell RG, Jaffe RB. Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. J Natl Cancer Inst. 2003;95:733-40. 35. Hur EM, Park YS, Lee BD, Jang IH, Kim HS, Kim TD, Suh PG, Ryu SH, Kim KT. Sensitization of epidermal growth factor-induced signaling by bradykinin is mediated by c-Src. Implications for a role of lipid microdomains. J Biol Chem. 2004;279:5852-60. 36. Ivanov AI, Nusrat A, Parkos CA. Endocytosis of epithelial apical junctional proteins by a clathrin-mediated pathway into a unique storage compartment. Mol Biol Cell. 2004;15:176-88. 37. Jalink K, Eichholtz T, Postma FR, van Corven EJ, Moolenaar WH. Lysophosphatidic acid induces neuronal shape changes via a novel, receptor-mediated signaling pathway: similarity to thrombin action. Cell Growth Differ 1993;4:247-55. 38. Jamora C, Fuchs E. Intercellular adhesion, signalling and the cytoskeleton. Nat Cell Biol 2002;4:E101-8. 39. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96. 40. Jourquin J, Yang N, Kam Y, Guess C, Quaranta V. Dispersal of epithelial cancer cell colonies by lysophosphatidic acid (LPA). J Cell Physiol 2006;206:337-46. 41. Kapus A, Di Ciano C, Sun J, Zhan X, Kim L, Wong TW, Rotstein OD. Cell volume-dependent phosphorylation of proteins of the cortical cytoskeleton and cell-cell contact sites. The role of Fyn and FER kinases. J Biol Chem. 2000;275:32289-98. 42. Keilhack H, Hellman U, van Hengel J, van Roy F, Godovac-Zimmermann J, Böhmer FD. The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin. J Biol Chem. 2000;275:26376-84. 43. Kitayama J, Shida D, Sako A, Ishikawa M, Hama K, Aoki J, Arai H, Nagawa H. Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma. Breast Cancer Res. 2004;6:R640-6. 44. Kim L, Wong TW. The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors. Mol Cell Biol 1995;15:4553-61. 45. Lilien J, Balsamo J. The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin. Curr Opin Cell Biol. 2005;17:459-65. 46. Luttrell DK, Luttrell LM. Not so strange bedfellows: G-protein-coupled receptors and Src family kinases. Oncogene 2004;23:7969-78. 47. Luttrell LM, Hawes BE, van Biesen T, Luttrell DK, Lansing TJ, Lefkowitz RJ. Role of c-Src tyrosine kinase in G protein-coupled receptor- and Gbetagamma subunit-mediated activation of mitogen-activated protein kinases. J Biol Chem 1996;271:19443-50. 48. Macpherson IR, Hooper S, Serrels A, McGarry L, Ozanne BW, Harrington K, Frame MC, Sahai E, Brunton VG. p120-catenin is required for the collective invasion of squamous cell carcinoma cells via a phosphorylation-independent mechanism. Oncogene. 2007 Aug 9;26(36):5214-28. 49. Mariner DJ, Davis MA, Reynolds AB. EGFR signaling to p120-catenin through phosphorylation at Y228. J Cell Sci 2004;117:1339-50. 50. Matsuyoshi N, Hamaguchi M, Taniguchi S, Nagafuchi A, Tsukita S, Takeichi M. Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J Cell Biol. 1992;118:703-14. 51. Moolenaar WH. Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res. 1999;253:230-8. 52. Mills GB, May C, McGill M, Roifman CM, Mellors A. A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. Cancer Res. 1988;48:1066-71. 53. Mills GB, May C, Hill M, Campbell S, Shaw P, Marks A. Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells. J Clin Invest 1990;86:851-5. 54. Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 2003;3:582-91. 55. Noren NK, Liu BP, Burridge K, Kreft B. p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol. 2000;150:567-80. 56. Owens DW, McLean GW, Wyke AW, Paraskeva C, Parkinson EK, Frame MC, Brunton VG. The catalytic activity of the Src family kinases is required to disrupt cadherin-dependent cell-cell contacts. Mol Biol Cell. 2000;11:51-64. 57. Ozawa M, Kemler R. Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. J Biol Chem 1998;273:6166-70. 58. Paterson AD, Parton RG, Ferguson C, Stow JL, Yap AS. Characterization of E-cadherin endocytosis in isolated MCF-7 and chinese hamster ovary cells: the initial fate of unbound E-cadherin. J Biol Chem. 2003;278:21050-7. 59. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108 60. Pébay A, Bonder CS, Pitson SM. Stem cell regulation by lysophospholipids. Prostaglandins Other Lipid Mediat. 2007;84:83-97. 61. Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C, Ullrich A. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature. 1999;402:884-8. 62. Piedra J, Miravet S, Castano J, Palmer HG, Heisterkamp N, Garcia de Herreros A, Dunach M. p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin interaction. Mol Cell Biol 2003;23:2287-97. 63. Pustilnik TB, Estrella V, Wiener JR, Mao M, Eder A, Watt MA, Bast RC, Jr., Mills GB. Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin Cancer Res 1999;5:3704-10. 64. Qian X, Karpova T, Sheppard AM, McNally J, Lowy DR. E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. Embo J 2004;23:1739-48. 65. Ren J, Xiao YJ, Singh LS, Zhao X, Zhao Z, Feng L, Rose TM, Prestwich GD, Xu Y. Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. Cancer Res. 2006;66:3006-14. 66. Reynolds AB, Herbert L, Cleveland JL, Berg ST, Gaut JR. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo. Oncogene 1992;7:2439-45. 67. Reynolds AB, Roesel DJ, Kanner SB, Parsons JT. Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol 1989;9:629-38. 68. Reynolds AB, Jenkins NA, Gilbert DJ, Copeland NG, Shapiro DN, Wu J, Daniel JM. The gene encoding p120cas, a novel catenin, localizes on human chromosome 11q11 (CTNND) and mouse chromosome 2 (Catns). Genomics 1996;31:127-9. 69. Rosato R, Veltmaat JM, Groffen J, Heisterkamp N. Involvement of the tyrosine kinase fer in cell adhesion. Mol Cell Biol 1998;18:5762-70. 70. Sawada K, Morishige K, Tahara M, Ikebuchi Y, Kawagishi R, Tasaka K, Murata Y. Lysophosphatidic acid induces focal adhesion assembly through Rho/Rho-associated kinase pathway in human ovarian cancer cells. Gynecol Oncol 2002;87:252-9. 71. Sawada K, Morishige K, Tahara M, Kawagishi R, Ikebuchi Y, Tasaka K, Murata Y. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho. Cancer Res 2002;62:6015-20. 72. Schulte KM, Beyer A, Köhrer K, Oberhäuser S, Röher HD. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int J Cancer. 2001;92:249-56. 73. Schwartz BM, Hong G, Morrison BH, Wu W, Baudhuin LM, Xiao YJ, Mok SC, Xu Y. Lysophospholipids increase interleukin-8 expression in ovarian cancer cells. Gynecol Oncol 2001;81:291-300. 74. Seidel B, Braeg S, Adler G, Wedlich D, Menke A. E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells. Oncogene. 2004;23:5532-42. 75. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219:983-5. 76. Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Oku N, Miyazawa K, Kitamura N, Takeichi M, Ito F. Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes Commun. 1994;:295-305. 77. Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Miyazawa K, Kitamura N, Johnson KR, Wheelock MJ, Matsuyoshi N, Takeichi M, et al. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J Cell Biol 1995;128:949-57. 78. Shida D, Watanabe T, Aoki J, Hama K, Kitayama J, Sonoda H, Kishi Y, Yamaguchi H, Sasaki S, Sako A, Konishi T, Arai H, Nagawa H. Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Lab Invest. 2004;84:1352-62. 79. Smicun Y, Gil O, Devine K, Fishman DA. S1P and LPA have an attachment-dependent regulatory effect on invasion of epithelial ovarian cancer cells. Gynecol Oncol. 2007;107:298-309. 80. Spinella F, Rosano L, Elia G, Di Castro V, Natali PG, Bagnato A. Endothelin-1 Stimulates Cyclooxygenase-2 Expression in Ovarian Cancer Cells Through Multiple Signaling Pathways: Evidence for Involvement of Transactivation of the Epidermal Growth Factor Receptor. J Cardiovasc Pharmacol 2004;44:S140-S3. 81. Tang H, Zhao ZJ, Huang XY, Landon EJ, Inagami T. Fyn kinase-directed activation of SH2 domain-containing protein-tyrosine phosphatase SHP-2 by Gi protein-coupled receptors in Madin-Darby canine kidney cells. J Biol Chem. 1999;274:12401-7. 82. Tice DA, Biscardi JS, Nickles AL, Parsons SJ. Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci U S A. 1999;96:1415-20. 83. Tokumura A, Fukuzawa K, Akamatsu Y, Yamada S, Suzuki T, Tsukatani H. Identification of vasopressor phospholipid in crude soybean lecithin. Lipids 1978;13:468-72. 84. Troyanovsky RB, Sokolov EP, Troyanovsky SM. Endocytosis of cadherin from intracellular junctions is the driving force for cadherin adhesive dimer disassembly. Mol Biol Cell. 2006;17:3484-93. 85. Wang P, Wu X, Chen W, Liu J, Wang X. The lysophosphatidic acid (LPA) receptors their expression and significance in epithelial ovarian neoplasms. Gynecol Oncol. 2007;104:714-20. 86. Wang GL, Wen ZQ, Xu WP, Wang ZY, Du XL, Wang F. Inhibition of lysophosphatidic acid receptor-2 expression by RNA interference decreases lysophosphatidic acid-induced urokinase plasminogen activator activation, cell invasion, and migration in ovarian cancer SKOV-3 cells. Croat Med J. 2008 Apr;49(2):175-81. 87. Westermann AM, Havik E, Postma FR, Beijnen JH, Dalesio O, Moolenaar WH, Rodenhuis S. Malignant effusions contain lysophosphatidic acid (LPA)-like activity. Ann Oncol. 1998;9:437-42. 88. Wildenberg GA, Dohn MR, Carnahan RH, Davis MA, Lobdell NA, Settleman J, Reynolds AB. p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 2006;127:1027-39. 89. Wong AS, Maines-Bandiera SL, Rosen B, Wheelock MJ, Johnson KR, Leung PC, Roskelley CD, Auersperg N. Constitutive and conditional cadherin expression in cultured human ovarian surface epithelium: influence of family history of ovarian cancer. Int J Cancer 1999;81:180-8. 90. Wong AS, Pelech SL, Woo MM, Yim G, Rosen B, Ehlen T, Leung PC, Auersperg N. Coexpression of hepatocyte growth factor-Met: an early step in ovarian carcinogenesis? Oncogene. 2001;20:1318-28. 91. Wu C, Cipollone J, Maines-Bandiera S, Tan C, Karan A, Auersperg N, Roskelley CD. The morphogenic function of E-cadherin-mediated adherens junctions in epithelial ovarian carcinoma formation and progression. Differentiation 2008;76:293-305. 92. Wu J, Cunnick JM. Trans-regulation of epidermal growth factor receptor by lysophosphatidic acid and G protein-coupled receptors. Biochim Biophys Acta 2002;1582:100-6. 93. Xia X, Mariner DJ, Reynolds AB. Adhesion-associated and PKC-modulated changes in serine/threonine phosphorylation of p120-catenin. Biochemistry. 2003;42:9195-204. 94. Xu Y, Casey G, Mills GB. Effect of lysophospholipids on signaling in the human Jurkat T cell line. J Cell Physiol 1995;163:441-50. 95. Xu Y, Shen Z, Wiper DW, Wu M, Morton RE, Elson P, Kennedy AW, Belinson J, Markman M, Casey G. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. Jama 1998;280:719-23. 96. Xu G, Craig AW, Greer P, Miller M, Anastasiadis PZ, Lilien J, Balsamo J. Continuous association of cadherin with beta-catenin requires the non-receptor tyrosine-kinase Fer. J Cell Sci. 2004;117:3207-19. 97. Yagi T, Takeichi M. Cadherin superfamily genes: functions, genomic organization, and neurologic diversity. Genes Dev. 2000;14:1169-80. 98. Yamashita H, Kitayama J, Shida D, Ishikawa M, Hama K, Aoki J, Arai H, Nagawa H. Differential expression of lysophosphatidic acid receptor-2 in intestinal and diffuse type gastric cancer. J Surg Oncol. 2006;93:30-5. 99. Yanagisawa M, Anastasiadis PZ. p120 catenin is essential for mesenchymal cadherin-mediated regulation of cell motility and invasiveness. J Cell Biol 2006;174:1087-96. 100. Yap AS, Niessen CM, Gumbiner BM. The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn. J Cell Biol. 1998;141:779-89. 101. Zondag GC, Reynolds AB, Moolenaar WH. Receptor protein-tyrosine phosphatase RPTPmu binds to and dephosphorylates the catenin p120(ctn). J Biol Chem. 2000;275:11264-9. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38015 | - |
| dc.description.abstract | 研究背景：水解磷脂酸(lysophosphatidic acid, LPA)是一種具有多樣生物功能的天然磷脂質，它能促進細胞增生、傷口癒合、以及神經細胞的突觸退縮等作用。此外，水解磷脂酸具有促進卵巢癌細胞生長的功能，在卵巢癌病患的腹水及血清中都含高濃度的脫脂磷脂酸。因此，水解磷脂酸被視為潛在性的卵巢癌生物標記。水解磷脂酸主要是藉由引發尿激素(urokinase)與基質金屬蛋白水解酶(MMP)的活性，同時促進應力纖維(stress fiber)及局部性黏著(focal adhesion)的形成，而達到促進卵巢癌細胞的移動。水解磷脂酸也會引發卵巢癌以外其他細胞株形態上的改變，包括：胞膜起皺褶(membrane ruffling)、板狀吸足生成(lamellipodia formation)、以及細胞與細胞相互分離。水解磷脂酸對卵巢癌細胞形態上的影響至今尚無定論。
研究目的：本研究針對水解磷脂酸在卵巢癌細胞形態上的影響，以及Src 家族蛋白質激酶與細胞黏連蛋白p120-catenin 的互動做探討，希望能藉由此研究，對水解磷脂酸促進卵巢癌細胞移動以及其分子機制，有更深入的了解。 研究題材及方法：本研究著重於水解磷脂酸對卵巢癌細胞間連結形態的探討，以及在卵巢癌細胞中，水解磷脂酸活化Src 家族蛋白質激酶對細胞間繫蛋白p120-catenin 的影響。並繼續探討水解磷脂酸活化上皮生長因子受體的機制，以及其對卵巢癌細胞間連結分離的影響。 研究結果：水解磷脂酸對具有混和上皮(epithelial)以及間質(mesenchymal)特性的卵巢癌細胞株SKOV3，引起細胞分散以及細胞黏連分離。本研究利用化學抑制劑PP2以及RNA干擾技術證明Src 家族蛋白質激酶為媒介水解磷脂酸此作用之重要蛋白。水解磷脂酸引發Src 家族蛋白質激酶活化，且促進其中之Fyn激酶與細胞連結蛋白p120-catenin的互動，進而調控與其他細胞黏連蛋白如β-catenin、α-catenin之穩定性。水解磷脂酸同時也活化其他的受體酪氨酸激酶(receptor tyrosine kinase)例如：上皮生長因子受體(EGFR)，本研究利用化學抑制劑AG 1478，證明上皮生長因子受體的活性對卵巢癌細胞間的連結分離扮演重要的角色。此外，藉由細胞間黏連蛋白質p120-catenin所提供之，被水解磷脂酸活化之Src 家族蛋白質激酶以及上皮生長因子受體，形成一個訊息傳遞整合的平台。 研究結論：水解磷脂酸對具有不同上皮特性的卵巢癌細胞株，造成不同的細胞分散以及細胞黏連分離的作用。水解磷脂酸經由活化Src 家族蛋白質激酶使卵巢癌細胞間的連結(cell-cell junction)分離，之後透過增加Src 家族蛋白質激酶之中的Fyn激酶與細胞間黏連蛋白質p120-catenin 的互動，影響p120-catenin 在細胞間連結的穩定性。水解磷脂酸與上皮生長因子受體之間的相互活化作用，也對於此一現象提供重要的調控機轉。 | zh_TW |
| dc.description.abstract | Abstract
Background: Lysophosphatidic acid (LPA) is a natural phospholipid with various biological functions, such as cell proliferation, wound healing, and neurite retraction. LPA is also known as “ovarian cancer activating factor”, which was found to present at high concentrations in the plasma and ascites of ovarian cancer patients and is regarded as a potential biomarker for epithelial ovarian cancer. LPA has been known to promote invasion and migration of ovarian cancer cells via induction of urokinase secretion, MMP2 activation, stress fiber formation, and focal adhesion assembly. In addition, LPA has been found to cause colony dispersal effects by inducing morphological changes including membrane ruffling, lamellipodia formation, cell-cell dissociation and single cell migration in other carcinoma cell lines. However, the LPA effects on cell-cell dissociation of ovarian cancer cells are still inconclusive. Objectives: This study is proposed to investigate the LPA-induced morphological changes of cell-cell junctions and the signaling pathways of Src family kinases involved in the protein interactions with adherens junction protein p120-catenin in ovarian cancer cells and to clarify the effects of LPA on cell motility and cell-cell junctions and to give an in depth insight to the molecular mechanism of ovarian cancer cell migration. Materials and Methods: This study focuses on the morphological effects of LPA on cell-cell junctions and the Src-signaling pathway involved in ovarian cancer cells. In addition, this study also investigates the cross-talk of LPA and EGFR pathway and its significance on LPA-induced junction dispersal in ovarian cancer cells. Results: LPA induced cell dispersal and half junction formation in ovarian cancer cell line SKOV3, which coexpresses epithelial (E-cadherin, cytokeratin) and mesenchymal (N-cadherin, vimentin) markers. Src-family kinases were involved in both processes, since the effects were abolished by the selective tyrosine kinase inhibitor PP2. LPA induced rapid and transient activation of Src family kinases, which were recruited to cell-cell junctions by increasing the association with the adherens junction protein p120-catenin. Src family kinase, Fyn, was identified as the key component associated with p120-catenin after LPA stimulation in SKOV3 cells and was responsible for the cell dispersal. An EGFR-transactivation was also involved in LPA-induced cell dispersal, which could be abolished by the EGFR inhibitor, AG 1478. Conclusions: LPA induces differential cell dispersal responses in ovarian cancer cell lines harboring different epithelial and mesenchymal phenotypes. LPA-induced junction dispersal in ovarian cancer cells is caused by activating Src family kinases following by increasing p120-catenin and Src family kinase, Fyn, association to interfere with the stability of p120-catenin at cell-cell junction. The cross-talking to other receptor tyrosine kinase pathway, such as EGFR, is also required for the LPA effects on junction dispersal in ovarian cancer cells. Key words: ovarian cancer, lysophosphatidic acid, cell adhesion, Src family kinase, EGFR | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:56:40Z (GMT). No. of bitstreams: 1 ntu-97-D93446004-1.pdf: 3876956 bytes, checksum: c2992220c4002532f902f59b084d9eac (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | Contents
口試委員會審定書………………………………………………………….……….I Dedication ………………………………………………………………...................III Acknowledgement .……………………………………………...………………...IV Abstract (Chinese).....................................................................................................V Abstract (English)……………………………….…………………….………….VII Chapter I. Introduction & Literature Review ………………........................1 1.1 The clinical presentation of epithelial ovarian cancer progression 1.2 The identification of lysophosphatidic acid as an important ovarian cancer promoting factor 1.3 The synthesis of lysophosphatidic acid 1.4 The lysophosphatidic acid signaling and physiological roles 1.5 Crosstalk between LPA signaling with receptor tyrosine kinases 1.6 The role of lysophosphatidic acid in ovarian carcinoma progression 1.7 The role of lysophosphatidic acid in other cancer models 1.8 The dynamic regulation of cell adhesion and cytoskeleton on cell motility 1.9 p120-catenin: the master regulator of cell adhesion Chapter II. Hypothesis & Specific Aims……………………………………...10 2.1 To investigate the morphological effects of LPA on cell dispersal and intercellular junction disruption in ovarian cancer cells. 2.2 To study Src-family kinase activities in LPA-induced intercellular junction dispersal in ovarian cancer cells. 2.3 To identify the network among p120-catenin, Src-family kinase, and EGFR as the modulating complex for LPA signaling. 2.4 To investigate how LPA influences the actin cytoskeleton by modifying p120-catenin. Chapter III. Materials and Method …………………………………………..11 3.1 Materials & Methods 3.2 Experimental Design Chapter IV. Results ……………………………………………………………….22 4.1 Differential effects of lysophosphatidic acid on cell dispersal on ovarian cancer cell lines mediated by LPA receptors 4.2 Lysophosphatidic acid induces intercellular junction dispersal and formation of “half-junctions” in ovarian cancer cells 4.3 Src family kinases are involved in LPA-induced ovarian cancer cell dispersal 4.4 Fyn kinase is the Src family kinase involved in LPA-induced cell dispersal 4.5 EGFR signaling is involved in LPA-induced ovarian cancer cell dispersal 4.6 LPA induces cell dispersal by modulating the actin cytoskeleton and Rho family GTPase Chapter V. Discussion…………………………………………………….………...79 5.1 The epithelial and mesenchymal phenotypes of ovarian cancer cells might determine the LPA response on cell dispersal. 5.2 LPA2 is involved in the LPA-induced SKOV3 cell dispersal. 5.3 The “half-junction” phenotype represents the transition phase during the dynamic process of cell dispersal. 5.4 A signal amplification loop between Src family kinase and EGFR occurs via p120-catenin at adherens junction during the process of LPA-induced ovarian cancer cell dispersal. 5.5 Tyrosine kinase Fyn plays a role in the regulation of ovarian cancer cell-cell adhesion by LPA. 5.6 A tyrosine phosphatase targeted to p120-catenin might be involved in the LPA-EGFR signaling loop. 5.7 p120-catenin participates in LPA-induced stress fiber disassembly and decreased RhoA activity. Chapter VI. Conclusions & Future Perspectives………………..…….…...91 References……………………………………………..…….……………….……...92 Figures Figure 1 .……………..……………………………….……….......................................24 Figure 2 .……..…………………………………………………………………………26 Figure 3 .……….……………………………………………………………………….30 Figure 4 .……..................................................................................................................32 Figure 5 .……..................................................................................................................34 Figure 6 .……..................................................................................................................36 Figure 7 .……..................................................................................................................40 Figure 8 .……..................................................................................................................42 Figure 9 .……..................................................................................................................44 Figure 10 .……................................................................................................................48 Figure 11 .……................................................................................................................50 Figure 12 .……................................................................................................................52 Figure 13 .……................................................................................................................56 Figure 14 .……................................................................................................................58 Figure 15 .……................................................................................................................60 Figure 16 .……................................................................................................................62 Figure 17 .……................................................................................................................64 Figure 18 .……................................................................................................................69 Figure 19 .……................................................................................................................71 Figure 20 .……................................................................................................................73 Figure 21 .……................................................................................................................75 Figure 22 .……................................................................................................................77 Appendix……………………………………………………………………….…...105 | |
| dc.language.iso | en | |
| dc.subject | 水解磷脂酸 | zh_TW |
| dc.subject | 上皮生長因子受體 | zh_TW |
| dc.subject | 細胞黏連Src 家族蛋白質激酶 | zh_TW |
| dc.subject | 卵巢癌細胞 | zh_TW |
| dc.subject | EGFR | en |
| dc.subject | Src family kinase | en |
| dc.subject | cell adhesion | en |
| dc.subject | lysophosphatidic acid | en |
| dc.subject | ovarian cancer | en |
| dc.title | 水解磷脂酸對人類卵巢癌SKOV3細胞分散及細胞連結分離之探討 | zh_TW |
| dc.title | The Role of Lysophosphatidic Acid in Ovarian Cancer SKOV3 Cell Dispersal and Junction Disruption | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 王淑美,謝長堯,王懷詩,劉鴻文 | |
| dc.subject.keyword | 卵巢癌細胞,水解磷脂酸,細胞黏連Src 家族蛋白質激酶,上皮生長因子受體, | zh_TW |
| dc.subject.keyword | ovarian cancer,lysophosphatidic acid,cell adhesion,Src family kinase,EGFR, | en |
| dc.relation.page | 105 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-06-10 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨生物細胞學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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