Regulation of the urokinase receptor (uPAR) by LDL receptor-related protein-1 (LRP1)

Current Pharmaceutical Design

Volumn 17, Issue 19, 2011, Pages 1962-1969

  Gonias, Steven L ^a   Gaultier, Alban ^a   Jo, Minji ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cell migration; Cell signaling; Endocytosis; LDL receptor related protein; LRP1; PAI 1; Plasminogen activator inhibitor 1; UPAR; Urokinase receptor; Urokinase type plasminogen activator; VLDL receptor

Indexed keywords

ADAM PROTEIN; ALPHA 2 MACROGLOBULIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN; APOLIPOPROTEIN E; CD11B ANTIGEN; CELL PROTEIN; CELL RECEPTOR; CLATHRIN; GROWTH FACTOR; INTEGRIN; LIGAND; LOW DENSITY LIPOPROTEIN RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; MATRIX PROTEIN; MEMBRANE PROTEIN; NEUROPILIN 1; PHOSPHATIDYLINOSITOL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEINASE; PROTEOME; RAC1 PROTEIN; RECEPTOR; SEMAPHORIN; STRESS ACTIVATED PROTEIN KINASE; SYNAPSIN I; TUMOR NECROSIS FACTOR RECEPTOR; UNINDEXED DRUG; UROKINASE RECEPTOR; VERY LOW DENSITY LIPOPROTEIN RECEPTOR;

ARTICLE; CANCER TISSUE; CELL DIFFERENTIATION; CELL MIGRATION; CELL SURVIVAL; CELL TYPE; DOWNSTREAM PROCESSING; ENDOCYTOSIS; EXTRACELLULAR MATRIX; GLIOBLASTOMA; HUMAN; LIGAND BINDING; MULTIGENE FAMILY; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER;

ANTINEOPLASTIC AGENTS; DRUG DISCOVERY; GENE EXPRESSION REGULATION; HUMANS; LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-1; NEOPLASMS; RECEPTORS, UROKINASE PLASMINOGEN ACTIVATOR;

EID: 80051682259     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211796718224     Document Type: Article

References (113)

1. Strickland DK, Gonias SL, Argraves WS. Diverse roles for the LDL receptor family. Trends Endocrinol Metab 2002; 13(2): 66-74.
2. Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK. Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. Embo J 1988; 7(13): 4119-4127.
3. Strickland DK, Ashcom JD, Williams S, Burgess WH, Migliorini M, Argraves WS. Sequence identity between the alpha 2- macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J Biol Chem 1990; 265(29): 17401-17404.
4. Gardai SJ, McPhillips KA, Frasch SC, et al. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 2005; 123(2): 321-334.
5. Ogden C, deCathelineau A, Hoffmann P, et al. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 2001; 194(6): 781-795.
6. Gaultier A, Wu X, Le Moan N, et al. Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis. J Cell Sci 2009; 122(Pt 8): 1155-1162.
7. Willnow TE, Moehring JM, Inocencio NM, Moehring TJ, Herz J. The low-density-lipoprotein receptor-related protein (LRP) is processed by furin in vivo and in vitro. Biochem J 1996; 313 (Pt 1): 71-76.
8. Mikhailenko I, Battery F, Migliorini M, et al. Recognition of alpha 2-macroglobulin by the low density lipoprotein receptor-related protein requires the cooperation of two ligand binding cluster regions. J Biol Chem 2001; 276(42): 39484-39491.
9. Li Y, Cam J, Bu G. Low-density lipoprotein receptor family: endocytosis and signal transduction. Mol Neurobiol 2001; 23(1): 53-67.
10. Li Y, Marzolo MP, van Kerkhof P, Strous GJ, Bu G. The YXXL motif, but not the two NPXY motifs, serves as the dominant endocytosis signal for low density lipoprotein receptor-related protein. J Biol Chem 2000; 275(22): 17187-17194.
11. Dickson RB, Willingham MC, Pastan I. alpha 2-macroglobulin adsorbed to colloidal gold: a new probe in the study of receptormediated endocytosis. J Cell Biol 1981; 89(1): 29-34.
12. Weaver AM, McCabe M, Kim I, Allietta MM, Gonias SL. Epidermal growth factor and platelet-derived growth factor-BB induce a stable increase in the activity of low density lipoprotein receptor-related protein in vascular smooth muscle cells by altering receptor distribution and recycling. J Biol Chem 1996; 271(40): 24894-24900.
13. Wu L, Gonias SL. The low-density lipoprotein receptor-related protein-1 associates transiently with lipid rafts. J Cell Biochem 2005; 96(5): 1021-1033.
14. Loukinova E, Ranganathan S, Kuznetsov S, et al. Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP). Evidence for integrated co-receptor function betwenn LRP and the PDGF. J Biol Chem 2002; 277(18): 15499-15506.
15. van Leuven F, Cassiman JJ, van den Berghe H. Primary amines inhibit recycling of alpha 2M receptors in fibroblasts. Cell 1980; 20(1): 37-43.
16. Kaplan J. Evidence for reutilization of surface receptors for alphamacroglobulin. protease complexes in rabbit alveolar macrophages. Cell 1980; 19(1): 197-205.
17. Ulery P, Beers J, Mikhailenko I, et al. Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimer's disease. J Biol Chem 2000; 275(10): 7410-7415.
18. Moestrup SK, Gliemann J, Pallesen G. Distribution of the alpha 2- macroglobulin receptor/low density lipoprotein receptor-related protein in human tissues. Cell Tissue Res 1992; 269(3): 375-382.
19. Hofmann SM, Zhou L, Perez-Tilve D, et al. Adipocyte LDL receptor-related protein-1 expression modulates postprandial lipid transport and glucose homeostasis in mice. J Clin Invest 2007; 117(11): 3271-3282.
20. Herz J, Clouthier DE, Hammer RE. LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. Cell 1992; 71(3): 411-421.
21. Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J. LRP: role in vascular wall integrity and protection from atherosclerosis. Science 2003; 300(5617): 329-332.
22. Overton C, Yancey P, Major A, Linton M, Fazio S. Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse. Circ Res 2007; 100(5): 670-677.
23. Gaultier A, Arandjelovic S, Niessen S, et al. Regulation of tumor necrosis factor receptor-1 and the IKK-NF-kappaB pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor. Blood 2008; 111(11): 5316-5325.
24. Shi Y, Mantuano E, Inoue G, Campana W, Gonias S. Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathway. Sci Signal 2009; 2(68): ra18.
25. Qiu Z, Hyman B, Rebeck G. Apolipoprotein E receptors mediate neurite outgrowth through activation of p44/42 mitogen-activated protein kinase in primary neurons. J Biol Chem 2004; 279(33): 34948-34956.
26. May P, Rohlmann A, Bock H, et al. Neuronal LRP1 functionally associates with postsynaptic proteins and is required for normal motor function in mice. Mol Cell Biol 2004; 24(20): 8872-8883.
27. Holtzman D, Pitas R, Kilbridge J, et al. Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line. Proc Natl Acad Sci U S A 1995; 92(21): 9480-9484.
28. Zhuo M, Holtzman D, Li Y, et al. Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation. J Neurosci 2000; 20(2): 542-549.
29. Lopes MB, Bogaev CA, Gonias SL, VandenBerg SR. Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptorrelated protein is increased in reactive and neoplastic glial cells. FEBS Lett 1994; 338(3): 301-305.
30. Campana WM, Li X, Dragojlovic N, Janes J, Gaultier A, Gonias SL. The low-density lipoprotein receptor-related protein is a prosurvival receptor in Schwann cells: possible implications in peripheral nerve injury. J Neurosci 2006 Oct 25; 26(43): 11197-11207.
31. Mantuano E, Inoue G, Li X, et al. The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of schwann cells by binding to low-density lipoprotein receptor-related protein. J Neurosci 2008; 28(45): 11571-11582.
32. Mantuano E, Jo M, Gonias S, Campana W. Low density lipoprotein receptor-related protein (LRP1) regulates Rac1 and RhoA reciprocally to control Schwann cell adhesion and migration. J Biol Chem 2010; 285(19): 14259-14266.
33. Li Y, Wood N, Parsons PG, Yellowlees D, Donnelly PK. Expression of alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein on surfaces of tumour cells: a study using flow cytometry. Cancer Lett 1997; 111(1-2): 199-205.
34. Gonias SL, LaMarre J, Crookston KP, et al. Alpha 2- macroglobulin and the alpha 2-macroglobulin receptor/LRP. A growth regulatory axis. Ann N Y Acad Sci 1994; 737: 273-290.
35. Meng H, Chen G, Zhang X, et al. Stromal LRP1 in lung adenocarcinoma predicts clinical outcome. Clin Cancer Res 2011 Feb 15.
36. Christensen L, Wiborg Simonsen AC, Heegaard CW, Moestrup SK, Andersen JA, Andreasen PA. Immunohistochemical localization of urokinase-type plasminogen activator, type-1 plasminogen-activator inhibitor, urokinase receptor and alpha(2)- macroglobulin receptor in human breast carcinomas. Int J Cancer 1996; 66(4): 441-452.
37. Song H, Li Y, Lee J, Schwartz AL, Bu G. Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res 2009; 69(3): 879-886.
38. Amos S, Mut M, diPierro CG, et al. Protein kinase C-alphamediated regulation of low-density lipoprotein receptor related protein and urokinase increases astrocytoma invasion. Cancer Res 2007 Nov 1; 67(21): 10241-10251.
39. Gopal U, Bohonowych JE, Lema-Tome C, et al. A Novel Extracellular Hsp90 Mediated Co-Receptor Function for LRP1 Regulates EphA2 Dependent Glioblastoma Cell Invasion. PLoS One 2011; 6(3): e17649.
40. Montel V, Gaultier A, Lester RD, Campana WM, Gonias SL. The low-density lipoprotein receptor-related protein regulates cancer cell survival and metastasis development. Cancer Res 2007; 67(20): 9817-9824.
41. Semenza GL. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med 2001; 7(8): 345-350.
42. Yang M, Huang H, Li J, Li D, Wang H. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation. FASEB J 2004; 18(15): 1920-1921.
43. Hayashi H, Campenot R, Vance D, Vance J. Apolipoprotein Econtaining lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptorrelated protein-1. J Neurosci 2007; 27(8): 1933-1941.
44. Mantuano E, Mukandala G, Li X, Campana W, Gonias S. Molecular dissection of the human alpha2-macroglobulin subunit reveals domains with antagonistic activities in cell signaling. J Biol Chem 2008; 283(29): 19904-19911.
45. Hu K, Yang J, Tanaka S, Gonias S, Mars W, Liu Y. Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression. J Biol Chem 2006; 281(4): 2120-2127.
46. Barnes H, Ackermann EJ, van der Geer P. V-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1. Oncogene 2003; 22(23): 3589-3597.
47. Gotthardt M, Trommsdorff M, Nevitt MF, et al. Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J Biol Chem 2000; 275(33): 25616-25624.
48. Lutz C, Nimpf J, Jenny M, et al. Evidence of functional modulation of the MEKK/JNK/cJun signaling cascade by the low density lipoprotein receptor-related protein (LRP). J Biol Chem 2002 Nov 8; 277(45): 43143-43151.
49. Hiesberger T, Trommsdorff M, Howell BW, et al. Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 1999; 24(2): 481-489.
50. Barberis L, Wary K, Fiucci G, et al. Distinct roles of the adaptor protein Shc and focal adhesion kinase in integrin signaling to ERK. J Biol Chem 2000; 275(47): 36532-36540.
51. Nguyen D, Webb D, Catling A, et al. Urokinase-type plasminogen activator stimulates the Ras/Extracellular signal-regulated kinase (ERK) signaling pathway and MCF-7 cell migration by a mechanism that requires focal adhesion kinase, Src, and Shc. Rapid dissociation of GRB2/Sps-Shc complex is associated with the transient phosphorylation of ERK in urokinase-treated cells. J Biol Chem 2000; 275(25): 19382-19388.
52. Bacskai B, Xia M, Strickland D, Rebeck G, Hyman B. The endocytic receptor protein LRP also mediates neuronal calcium signaling via N-methyl-D-aspartate receptors. Proc Natl Acad Sci U S A 2000; 97(21): 1155111556.
53. Makarova A, Bercury K, Adams K, et al. The LDL receptor-related protein can form homo-dimers in neuronal cells. Neurosci Lett 2008; 442(2): 91-95.
54. Rebeck G. Nontraditional signaling mechanisms of lipoprotein receptors. Sci Signal 2009; 2(68): pe28.
55. Gorovoy M, Gaultier A, Campana W, Firestein G, Gonias S. Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages. J Leukoc Biol 2010; 88(4): 769-778.
56. Polavarapu R, An J, Zhang C, Yepes M. Regulated intramembrane proteolysis of the low-density lipoprotein receptor-related protein mediates ischemic cell death. Am J Pathol 2008; 172(5): 1355-1362.
57. Cao C, Lawrence D, Li Y, et al. Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration. EMBO J 2006; 25(9): 1860-1870.
58. Hamik A, Setiadi H, Bu G, McEver R, Morrissey J. Downregulation of monocyte tissue factor mediated by tissue factor pathway inhibitor and the low density lipoprotein receptor-related protein. J Biol Chem 1999; 274(8): 4962-4969.
59. Pietrzik CYIS, Jaeger S, Busse T, Weggen S, Koo E. FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein. J Neurosci 2004; 24(17): 4259-4265.
60. Gaultier A, Simon G, Niessen S, et al. LDL receptor-related protein 1 regulates the abundance of diverse cell-signaling proteins in the plasma membrane proteome. J Proteome Res 2010; 9(12): 6689-6695.
61. Nykjaer A, Kjøller L, Cohen R, et al. Regions involved in binding of urokinase-type-1 inhibitor complex and pro-urokinase to the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that the urokinase receptor protects pro-urokinase against binding to the endocytic receptor. J Biol Chem 1994; 269(41): 25668-25676.
62. Kounnas M, Henkin J, Argraves W, Strickland D. Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor mediates cellular uptake of pro-urokinase. J Biol Chem 1993; 268(29): 21862-21867.
63. Conese M, Nykjaer A, Petersen CM, et al. alpha-2 Macroglobulin receptor/Ldl receptor-related protein(Lrp)-dependent internalization of the urokinase receptor. J Cell Biol 1995; 131(6 Pt 1): 1609-1622.
64. Czekay R, Aertgeerts K, Curriden S, Loskutoff D. Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. J Cell Biol 2003; 160(5): 781-791.
65. Webb DJ, Nguyen DH, Sankovic M, Gonias SL. The very low density lipoprotein receptor regulates urokinase receptor catabolism and breast cancer cell motility in vitro. J Biol Chem 1999; 274(11): 7412-7420.
66. Nykjaer A, Conese M, Christensen E, et al. Recycling of the urokinase receptor upon internalization of the uPA: serpin complexes. EMBO J 1997; 16(10): 2610-2620.
67. Prager GW, Breuss JM, Steurer S, et al. Vascular endothelial growth factor receptor-2-induced initial endothelial cell migration depends on the presence of the urokinase receptor. Circ Res 2004; 94(12): 1562-1570.
68. Binder BR, Mihaly J, Prager GW. UPAR-uPA-PAI-1 interactions and signaling: a vascular biologist's view. Thromb Haemost 2007; 97(3): 336-342.
69. Weaver AM, Hussaini IM, Mazar A, Henkin J, Gonias SL. Embryonic fibroblasts that are genetically deficient in low density lipoprotein receptor-related protein demonstrate increased activity of the urokinase receptor system and accelerated migration on vitronectin. J Biol Chem 1997 May 30; 272(22): 14372-14379.
70. Gaultier A, Hollister M, Reynolds I, Hsieh E, Gonias S. LRP1 regulates remodeling of the extracellular matrix by fibroblasts. Matrix Biol 2010; 29(1): 22-30.
71. Zhang J, Sakthivel R, Kniss D, Graham C, Strickland D, McCrae K. The low density lipoprotein receptor-related protein/alpha2- macroglobulin receptor regulates cell surface plasminogen activator activity on human trophoblast cells. J Biol Chem 1998; 273(48): 32273-32280.
72. Blasi F, Carmeliet P. UPAR: a versatile signaling orchestrator. Nat Rev Mol Cell Biol 2002 December; 3(12): 932-943.
73. Nguyen D, Catling A, Webb D, et al. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J Cell Biol 1999 July 12; 146(1): 149-164.
74. Nguyen D, Hussaini I, Gonias S. Binding of urokinase-type plasminogen activator to its receptor in MCF-7 cells activates extracellular signal-regulated kinase 1 and 2 which is required for increased cellular motility. J Biol Chem 1998; 273(14): 5802-8507.
75. Shushakova N, Tkachuk N, Dangers M, et al. Urokinase-induced activation of the gp130/Tyk2/Stat3 pathway mediates a proinflammatory effect in human mesangial cells via expression of the anaphylatoxin C5a receptor. J Cell Sci 2005; 118(Pt 12): 2743-2753.
76. Fuhrman B, Gantman A, Khateeb J, et al. Urokinase activates macrophage PON2 gene transcription via the PI3K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-beta. Cardiovasc Res 2009; 84(1): 145-154.
77. Alfano D, Iaccarino I, Stoppelli M. Urokinase signaling through its receptor protects against anoikis by increasing BCL-xL expression levels. J Biol Chem 2006; 281(26): 17758-17767.
78. Lester R, Jo M, Montel V, Takimoto S, Gonias S. UPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cells. J Cell Biol 2007; 178(3): 425-436.
79. Ma Z, Thomas KS, Webb DJ, et al. Regulation of Rac1 activation by the low density lipoprotein receptor-related protein. J Cell Biol 2002 Dec 23; 159(6): 1061-1070.
80. Smith H, Marra P, Marshall C. UPAR promotes formation of the p130Cas-Crk complex to activate Rac through DOCK180. J Cell Biol 2008; 182(4): 777-790.
81. Kjøller L, Hall A. Rac mediates cytoskeletal rearrangements and increased cell motility induced by urokinase-type plasminogen activator receptor binding to vitronectin. J Cell Biol 2001; 152(6): 1145-1157.
82. Sidenius N, Blasi F. Domain 1 of the urokinase receptor (uPAR) is required for uPAR-mediated cell binding to vitronectin. FEBS Lett 2000; 470(1): 40-46.
83. Carriero M, del Vecchio S, Franco P, et al. Vitronectin binding to urokinase receptor in human breast cancer. Clin Cancer Res 1997; 3(8): 1299-1308.
84. Liang O, Chavakis T, Kanse S, Preissner K. Ligand binding regions in the receptor for urokinase-type plasminogen activator. J Biol Chem 2001; 276(31): 28946-28953.
85. Jo M, Thomas K, O'Donnell D, Gonias S. Epidermal growth factor receptor-dependent and -independent cell-signaling pathways originating from the urokinase receptor. J Biol Chem 2003; 278(3): 1642-1646.
86. Ryan R, Doyle A, Yamada K. Random versus directionally persistent cell migration. Nat Rev Mol Cell Biol 2009; 10(8): 538-549.
87. Degryse B, Sier C, Resnati M, Conese M, Blasi F. PAI-1 inhibits urokinase-induced chemotaxis by internalizing the urokinase receptor. FEBS Lett 2001; 505(2): 249-254.
88. Zhu Y, Bujo H, Yamazaki H, et al. LR11, an LDL receptor gene family member, is a novel regulator of smooth muscle cell migration. Circ Res 2004; 94(6): 752-758.
89. Li Y, Knisely JM, Lu W, et al. Low density lipoprotein (LDL) receptor-related protein 1B impairs urokinase receptor regeneration on the cell surface and inhibits cell migration. J Biol Chem 2002; 277(44): 42366-42371.
90. Nykjaer A, Christensen EI, Vorum H, et al. Mannose 6- phosphate/insulin-like growth factor-II receptor targets the urokinase receptor to lysosomes via a novel binding interaction. J Cell Biol 1998; 141(3): 815-828.
91. Schiller HB, Szekeres A, Binder BR, Stockinger H, Leksa V. Mannose 6-phosphate/insulin-like growth factor 2 receptor limits cell invasion by controlling alphaVbeta3 integrin expression and proteolytic processing of urokinase-type plasminogen activator receptor. Mol Biol Cell 2009; 20(3): 745-756.
92. Leksa V, Godar S, Cebecauer M, et al. The N terminus of mannose 6-phosphate/insulin-like growth factor 2 receptor in regulation of fibrinolysis and cell migration. J Biol Chem 2002 Oct 25; 277(43): 40575-40582.
93. Engelholm LH, Ingvarsen S, Jurgensen HJ, et al. The collagen receptor uPARAP/Endo180. Front Biosci 2009; 14: 2103-2114.
94. Sturge J, Wienke D, East L, Jones GE, Isacke CM. GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis. J Cell Biol 2003; 162(5): 789-794.
95. Gaultier A, Salicioni AM, Arandjelovic S, Gonias SL. Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1. J Biol Chem 2006; 281(11): 7332-7340.
96. Czekay RP, Kuemmel TA, Orlando RA, Farquhar MG. Direct binding of occupied urokinase receptor (uPAR) to LDL receptorrelated protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity. Mol Biol Cell 2001; 12(5): 1467-1479.
97. Webb D, Thomas K, Gonias S. Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signaling and thereby promotes MCF-7 cell growth. J Cell Biol 2001; 152(4): 741-752.
98. Croucher D, Saunders DN, Ranson M. The urokinase/PAI-2 complex: a new high affinity ligand for the endocytosis receptor low density lipoprotein receptor-related protein. J Biol Chem 2006; 281(15): 10206-10213.
99. Prager GW, Mihaly J, Brunner PM, Koshelnick Y, Hoyer-Hansen G, Binder BR. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein. Blood 2009; 113(6): 1383-1390.
100. Andreasen PA, Kjoller L, Christensen L, Duffy MJ. The urokinasetype plasminogen activator system in cancer metastasis: a review. Int J Cancer 1997; 72(1): 1-22.
101. Pappot H, Gardsvoll H, Romer J, et al. Plasminogen activator inhibitor type 1 in cancer: therapeutic and prognostic implications. Biol Chem Hoppe Seyler 1995; 376(5): 259-267.
102. Mazar AP, Henkin J, Goldfarb RH. The urokinase plasminogen activator system in cancer: implications for tumor angiogenesis and metastasis. Angiogenesis 1999; 3(1): 15-32.
103. Aguirre-Ghiso J, Kovalski K, Ossowski L. Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 1999; 147(1): 89-104.
104. Jo M, Lester R, Montel V, Eastman B, Takimoto S, Gonias S. Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling. J Biol Chem 2009; 284(34): 22825-22833.
105. Jo M, Eastman B, Webb D, Stoletov K, Klemke R, Gonias S. Cell signaling by urokinase-type plasminogen activator receptor induces stem cell-like properties in breast cancer cells. Cancer Res 2010; 70(21): 8948-8958.
106. Chen Z, Lin L, Huai Q, Huang M. Challenges for drug discovery - a case study of urokinase receptor inhibition. Comb Chem High Throughput Screen 2009; 12(10): 961-967.
107. Gondi CS, Lakka SS, Dinh DH, Olivero WC, Gujrati M, Rao JS. Intraperitoneal injection of a hairpin RNA-expressing plasmid targeting urokinase-type plasminogen activator (uPA) receptor and uPA retards angiogenesis and inhibits intracranial tumor growth in nude mice. Clin Cancer Res 2007; 13(14): 4051-4060.
108. Kunigal S, Lakka SS, Gondi CS, Estes N, Rao JS. RNAi-mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease-9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth. Int J Cancer 2007; 121(10): 2307-2316.
109. Gorantla B, Asuthkar S, Rao JS, Patel J, Gondi CS. Suppression of the uPAR-uPA System Retards Angiogenesis, Invasion and in vivo Tumor Development in Pancreatic Cancer Cells. Mol Cancer Res 2011 Mar 9.
110. Van Buren G, 2nd, Gray MJ, Dallas NA, et al. Targeting the urokinase plasminogen activator receptor with a monoclonal antibody impairs the growth of human colorectal cancer in the liver. Cancer 2009; 115(14): 3360-3368.
111. Rabbani SA, Ateeq B, Arakelian A, et al. An anti-urokinase plasminogen activator receptor antibody (ATN-658) blocks prostate cancer invasion, migration, growth, and experimental skeletal metastasis in vitro and in vivo. Neoplasia 2010; 12(10): 778-788.
112. Kenny HA, Leonhardt P, Ladanyi A, et al. Targeting the urokinase plasminogen activator receptor inhibits ovarian cancer metastasis. Clin Cancer Res 2011; 17(3): 459-471.
113. Goldstein LJ, Stemmer SM, Schmalfeldt B, et al. Phase II, twoarm, double-blind, multicenter, randomized study of the combination of oral WX-671 plus capecitabine versus capecitabine in first-line HER2-negative metastatic breast cancer (MBC). J Clin Oncol 2010; 28(15s): abstr TPS131.