Epidermal growth factor receptor (EGFR) crosstalks in liver cancer

Cancers

Volumn 3, Issue 2, 2011, Pages 2444-2461

  Berasain, Carmen ^a   Latasa, María Ujue ^a   Urtasun, Raquel ^a   Goñi, Saioa ^a   Elizalde, María ^a   Garcia Irigoyen, Oihane ^a   Azcona, María ^a   Prieto, Jesús ^a,b   Ávila, Matías ^a  

^a UNIVERSITY OF NAVARRA   (Spain)

^b UNIVERSITY CLINIC OF NAVARRA   (Spain)

Author keywords

A desintegrin and metalloprotease (ADAM); G protein coupled receptor (GPCR); Growth factor receptor; Transactivation

Indexed keywords

ADAM PROTEIN; AUTOTAXIN; CYCLOOXYGENASE 2; ENDOTHELIN 1; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; EPIDERMAL GROWTH FACTOR RECEPTOR VIII; FAS ANTIGEN; G PROTEIN COUPLED RECEPTOR; LYSOPHOSPHATIDIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROSTAGLANDIN E2; PROTEIN ARGININE METHYLTRANSFERASE; PROTEIN ARGININE METHYLTRANSFERASE 5; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; SOMATOSTATIN RECEPTOR; SORAFENIB; STROMAL CELL DERIVED FACTOR 1; TRANSFORMING GROWTH FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME; UNCLASSIFIED DRUG; UNINDEXED DRUG; UROKINASE RECEPTOR; VERY LATE ACTIVATION ANTIGEN 5;

APOPTOSIS; AUTOPHOSPHORYLATION; CELL PROLIFERATION; DIMERIZATION; DRUG RESISTANCE; HUMAN; INTRACELLULAR SIGNALING; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MALIGNANT TRANSFORMATION; NONHUMAN; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN VARIANT; REVIEW; SIGNAL TRANSDUCTION; TRANSACTIVATION; TRIPLE MEMBRANE PASSING SIGNAL;

EID: 79959703984     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers3022444     Document Type: Review

References (112)

1. El-Serag, H.B.; Rudolph, K.L. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132, 2557-2576.
2. Nordenstedt, H.; White, D.L.; El-Serag, H.B. The changing pattern of epidemiology in hepatocellular carcinoma. Dig. Liver Dis. 2010, 42 (Suppl. 3), S206-S214.
3. Avila, M.A.; Berasain, C.; Sangro, B.; Prieto, J. New therapies for hepatocellular carcinoma. Oncogene 2006, 25, 3866-3884.
4. Whittaker, S.; Marais, R.; Zhu, A.X. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010, 29, 4989-5005.
5. Breuhahn, K.; Longerich, T.; Schirmacher, P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 2006, 25, 3787-3800.
6. Porta, C.; Paglino, C. Medical treatment of unresectable hepatocellular carcinoma: Going beyond sorafenib. World J. Hepatol. 2010, 2, 103-113.
7. Zandi, R.; Larsen, A.B.; Andersen, P.; Stockhausen, M.T.; Poulsen, H.S. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell Signal. 2007, 19, 2013-2023.
8. Kira, S.; Nakanishi, T.; Suemori, S.; Kitamoto, M.; Watanabe, Y.; Kajiyama, G. Expression of transforming growth factor alpha and epidermal growth factor receptor in human hepatocellular carcinoma. Liver 1997, 17, 177-182.
9. Daveau, M.; Scotte, M.; Francois, A.; Coulouarn, C.; Ros, G.; Tallet, Y.; Hiron, M.; Hellot, M.F.; Salier, J.P. Hepatocyte growth factor, transforming growth factor alpha, and their receptors as combined markers of prognosis in hepatocellular carcinoma. Mol. Carcinog. 2003, 36, 130-141.
10. Prenzel, N.; Zwick, E.; Leserer, M.; Ullrich, A. Tyrosine kinase signalling in breast cancer. Epidermal growth factor receptor: Convergence point for signal integration and diversification. Breast Cancer Res. 2000, 2, 184-190.
11. Berasain, C.; Perugorria, M.J.; Latasa, M.U.; Castillo, J.; Goni, S.; Santamaria, M.; Prieto, J.; Avila, M.A. The epidermal growth factor receptor: A link between inflammation and liver cancer. Exp. Biol. Med. (Maywood) 2009, 234, 713-725.
12. Ohtsu, H.; Dempsey, P.J.; Eguchi, S. ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am. J. Physiol. Cell Physiol. 2006, 291, C1-C10.
13. Hackel, P.O.; Zwick, E.; Prenzel, N.; Ullrich, A. Epidermal growth factor receptors: Critical mediators of multiple receptor pathways. Curr. Opin. Cell Biol. 1999, 11, 184-189.
14. Moghal, N.; Sternberg, P.W. Multiple positive and negative regulators of signaling by the EGF-receptor. Curr. Opin. Cell Biol. 1999, 11, 190-196.
15. Liebmann, C. EGF receptor activation by GPCRs: An universal pathway reveals different versions. Mol. Cell. Endocrinol. 2011, 331, 222-231.
16. Saito, Y.; Haendeler, J.; Hojo, Y.; Yamamoto, K.; Berk, B.C. Receptor heterodimerization: Essential mechanism for platelet-derived growth factor-induced epidermal growth factor receptor transactivation. Mol. Cell. Biol. 2001, 21, 6387-6394.
17. Morgillo, F.; Woo, J.K.; Kim, E.S.; Hong, W.K.; Lee, H.Y. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Res. 2006, 66, 10100-10111
18. Almendro, V.; Garcia-Recio, S.; Gascon, P. Tyrosine kinase receptor transactivation associated to G protein-coupled receptors. Curr. Drug Targets 2010, 11, 1169-1180.
19. Yamauchi, T.; Ueki, K.; Tobe, K.; Tamemoto, H.; Sekine, N.; Wada, M.; Honjo, M.; Takahashi, M.; Takahashi, T.; Hirai, H. et al. Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone. Nature 1997, 390, 91-96.
20. Zhu, A.X.; Stuart, K.; Blaszkowsky, L.S.; Muzikansky, A.; Reitberg, D.P.; Clark, J.W.; Enzinger, P.C.; Bhargava, P.; Meyerhardt, J.A.; Horgan, K.; et al.Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 2007, 110, 581-589.
21. Llovet, J.M.; Bruix, J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 2008, 48, 1312-1327.
22. Berasain, C.; Castillo, J.; Prieto, J.; Avila, M.A. New molecular targets for hepatocellular carcinoma: The ErbB1 signaling system. Liver Int. 2007, 27, 174-185.
23. Citri, A.; Yarden, Y. EGF-ERBB signalling: Towards the systems level. Nat. Rev. Mol. Cell Biol. 2006, 7, 505-516.
24. Sibilia, M.; Kroismayr, R.; Lichtenberger, B.M.; Natarajan, A.; Hecking, M.; Holcmann, M. The epidermal growth factor receptor: From development to tumorigenesis. Differentiation 2007, 75, 770-787.
25. Krall, J.A.; Beyer, E.M.; MacBeath, G. High- and low-affinity epidermal growth factor receptor-ligand interactions activate distinct signaling pathways. PLoS One 2011, 6, e15945.
26. Wilson, K.J.; Gilmore, J.L.; Foley, J.; Lemmon, M.A.; Riese, D.J., Functional selectivity of EGF family peptide growth factors: Implications for cancer. Pharmacol. Ther. 2009, 122, 1-8.
27. Jorissen, R.N.; Walker, F.; Pouliot, N.; Garrett, T.P.; Ward, C.W.; Burgess, A.W. Epidermal growth factor receptor: Mechanisms of activation and signalling. Exp. Cell Res. 2003, 284, 31-53.
28. Harris, R.C.; Chung, E.; Coffey, R.J. EGF receptor ligands. Exp. Cell Res. 2003, 284, 2-13.
29. Berasain, C.; Castillo, J.; Perugorria, M.J.; Prieto, J.; Avila, M.A. Amphiregulin: A new growth factor in hepatocarcinogenesis. Cancer Lett. 2007, 254, 30-41.
30. Higashiyama, S.; Iwabuki, H.; Morimoto, C.; Hieda, M.; Inoue, H.; Matsushita, N. Membrane-anchored growth factors, the epidermal growth factor family: Beyond receptor ligands. Cancer Sci. 2008, 99, 214-220.
31. Schneider, M.R.; Wolf, E. The epidermal growth factor receptor ligands at a glance. J. Cell. Physiol. 2009, 218, 460-466.
32. Blobel, C.P.; Carpenter, G.; Freeman, M. The role of protease activity in ErbB biology. Exp. Cell Res. 2009, 315, 671-682.
33. Natarajan, A.; Wagner, B.; Sibilia, M. The EGF receptor is required for efficient liver regeneration. Proc. Natl. Acad. Sci. USA 2007, 104, 17081-17086.
34. Berasain, C.; Garcia-Trevijano, E.R.; Castillo, J.; Erroba, E.; Lee, D.C.; Prieto, J.; Avila, M.A. Amphiregulin: An early trigger of liver regeneration in mice. Gastroenterology 2005, 128, 424-432.
35. Mitchell, C.; Nivison, M.; Jackson, L.F.; Fox, R.; Lee, D.C.; Campbell, J.S.; Fausto, N. Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration. J. Biol. Chem. 2005, 280, 2562-2568.
36. Deaciuc, I.V.; DSouza, N.B.; Burikhanov, R.; Lee, E.Y.; Tarba, C.N.; McClain, C.J.; de Villiers, W.J. Epidermal growth factor protects the liver against alcohol-induced injury and sensitization to bacterial lipopolysaccharide. Alcohol. Clin. Exp. Res. 2002, 26, 864-874.
37. Berasain, C.; Garcia-Trevijano, E.R.; Castillo, J.; Erroba, E.; Santamaria, M.; Lee, D.C.; Prieto, J.; Avila, M.A. Novel role for amphiregulin in protection from liver injury. J. Biol. Chem. 2005, 280, 19012-19020.
38. Khai, N.C.; Takahashi, T.; Ushikoshi, H.; Nagano, S.; Yuge, K.; Esaki, M.; Kawai, T.; Goto, K.; Murofushi, Y.; Fujiwara, T.; et al. In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and induces liver regeneration in mice: A comparative study to HGF. J. Hepatol. 2006, 44, 1046-1054.
39. Castillo, J.; Erroba, E.; Perugorria, M.J.; Santamaria, M.; Lee, D.C.; Prieto, J.; Avila, M.A.; Berasain, C. Amphiregulin contributes to the transformed phenotype of human hepatocellular carcinoma cells. Cancer Res. 2006, 66, 6129-6138.
40. Castillo, J.; Goni, S.; Latasa, M.U.; Perugorria, M.J.; Calvo, A.; Muntane, J.; Bioulac-Sage, P.; Balabaud, C.; Prieto, J.; Avila, M.A.; Berasain, C. Amphiregulin induces the alternative splicing of p73 into its oncogenic isoform DeltaEx2p73 in human hepatocellular tumors. Gastroenterology 2009, 137, 1805-1815.
41. Hopfner, M.; Sutter, A.P.; Huether, A.; Schuppan, D.; Zeitz, M.; Scherubl, H. Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma. J. Hepatol. 2004, 41, 1008-1016.
42. Huether, A.; Hopfner, M.; Sutter, A.P.; Schuppan, D.; Scherubl, H. Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics. J. Hepatol. 2005, 43, 661-669.
43. Borlak, J.; Meier, T.; Halter, R.; Spanel, R.; Spanel-Borowski, K. Epidermal growth factor-induced hepatocellular carcinoma: Gene expression profiles in precursor lesions, early stage and solitary tumours. Oncogene 2005, 24, 1809-1819.
44. Webber, E.M.; Wu, J.C.; Wang, L.; Merlino, G.; Fausto, N. Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice. Am. J. Pathol. 1994, 145, 398-408.
45. Russell, W.E.; Kaufmann, W.K.; Sitaric, S.; Luetteke, N.C.; Lee, D.C. Liver regeneration and hepatocarcinogenesis in transforming growth factor-alpha-targeted mice. Mol. Carcinog. 1996, 15, 183-189.
46. Schiffer, E.; Housset, C.; Cacheux, W.; Wendum, D.; Desbois-Mouthon, C.; Rey, C.; Clergue, F.; Poupon, R.; Barbu, V.; Rosmorduc, O. Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. Hepatology 2005, 41, 307-314.
47. Su, M.C.; Lien, H.C.; Jeng, Y.M. Absence of epidermal growth factor receptor exon 18-21 mutation in hepatocellular carcinoma. Cancer Lett. 2005, 224, 117-121.
48. Zhou, M.; Gong, B.; Gu, J.; Li, Z. EGFRvIII mRNA detection in the serum of patients with hepatocellular carcinoma. Liver Int. 2010, 30, 925-927.
49. Wang, H.; Jiang, H.; Zhou, M.; Xu, Z.; Liu, S.; Shi, B.; Yao, X.; Yao, M.; Gu, J.; Li, Z. Epidermal growth factor receptor vIII enhances tumorigenicity and resistance to 5-fluorouracil in human hepatocellular carcinoma. Cancer Lett. 2009, 279, 30-38
50. Jiang, H.; Wang, H.; Tan, Z.; Hu, S.; Shi, B.; Yang, L.; Li, P.; Gu, J.; Li, Z. Growth suppression of human hepatocellular carcinoma xenografts by a monoclonal antibody CH12 directed to epidermal growth factor receptor variant III. J. Biol. Chem. 2011, 286, 5913-5920.
51. Bekaii-Saab, T.; Williams, N.; Plass, C.; Calero, M.V.; Eng, C. A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma. BMC Cancer 2006, 6, 278.
52. Ito, Y.; Takeda, T.; Sakon, M.; Tsujimoto, M.; Higashiyama, S.; Noda, K.; Miyoshi, E.; Monden, M.; Matsuura, N. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br. J. Cancer 2001, 84, 1377-1383.
53. Liu, J.; Ahiekpor, A.; Li, L.; Li, X.; Arbuthnot, P.; Kew, M.; Feitelson, M.A. Increased expression of ErbB-2 in liver is associated with hepatitis B× antigen and shorter survival in patients with liver cancer. Int. J. Cancer 2009, 125, 1894-1901.
54. Inui, Y.; Higashiyama, S.; Kawata, S.; Tamura, S.; Miyagawa, J.; Taniguchi, N.; Matsuzawa, Y. Expression of heparin-binding epidermal growth factor in human hepatocellular carcinoma. Gastroenterology 1994, 107, 1799-1804.
55. Chung, Y.H.; Kim, J.A.; Song, B.C.; Lee, G.C.; Koh, M.S.; Lee, Y.S.; Lee, S.G.; Suh, D.J. Expression of transforming growth factor-alpha mRNA in livers of patients with chronic viral hepatitis and hepatocellular carcinoma. Cancer 2000, 89, 977-982.
56. Ding, X.; Yang, L.Y.; Huang, G.W.; Wang, W.; Lu, W.Q. ADAM17 mRNA expression and pathological features of hepatocellular carcinoma. World J. Gastroenterol. 2004, 10, 2735-2739.
57. Olayioye, M.A.; Neve, R.M.; Lane, H.A.; Hynes, N.E. The ErbB signaling network: Receptor heterodimerization in development and cancer. EMBO J. 2000, 19, 3159-3167.
58. Lenferink, A.E.; Pinkas-Kramarski, R.; van de Poll, M.L.; van Vugt, M.J.; Klapper, L.N.; Tzahar, E.; Waterman, H.; Sela, M.; van Zoelen, E.J.; Yarden, Y. Differential end ocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J. 1998, 17, 3385-3397.
59. Karunagaran, D.; Tzahar, E.; Beerli, R.R.; Chen, X.; Graus-Porta, D.; Ratzkin, B.J.; Seger, R.; Hynes, N.E.; Yarden, Y. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer. EMBO J. 1996, 15, 254-264.
60. Habib, A.A.; Hognason, T.; Ren, J.; Stefansson, K.; Ratan, R.R. The epidermal growth factor receptor associates with and recruits phosphatidylinositol 3-kinase to the platelet-derived growth factor beta receptor. J. Biol. Chem. 1998, 273, 6885-6891.
61. Jo, M.; Stolz, D.B.; Esplen, J.E.; Dorko, K.; Michalopoulos, G.K.; Strom, S.C. Cross-talk between epidermal growth factor receptor and c-Met signal pathways in transformed cells. J. Biol. Chem. 2000, 275, 8806-8811.
62. Watt, H.L.; Kharmate, G.D.; Kumar, U. Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: Agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cells. Cell Signal. 2009, 21, 428-439.
63. Campbell, J.S.; Hughes, S.D.; Gilbertson, D.G.; Palmer, T.E.; Holdren, M.S.; Haran, A.C.; Odell, M.M.; Bauer, R.L.; Ren, H.P.; Haugen, H.S.; et al. Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 2005, 102, 3389-3394.
64. Karamouzis, M.V.; Konstantinopoulos, P.A.; Papavassiliou, A.G. Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR inhibitors. Lancet Oncol. 2009, 10, 709-717
65. Fischer, O.M.; Giordano, S.; Comoglio, P.M.; Ullrich, A. Reactive oxygen species mediate Met eceptor transactivation by G protein-coupled receptors and the epidermal growth factor receptor in human carcinoma cells. J. Biol. Chem. 2004, 279, 28970-28978.
66. Scheving, L.A.; Stevenson, M.C.; Taylormoore, J.M.; Traxler, P.; Russell, W.E. Integral role of the EGF receptor in HGF-mediated hepatocyte proliferation. Biochem. Biophys. Res. Commun. 2002, 290, 197-203.
67. Samonakis, D.N.; Notas, G.; Christodoulakis, N.; Kouroumalis, E.A. Mechanisms of action and resistance of somatostatin analogues for the treatment of hepatocellular carcinoma: A message not well taken. Dig. Dis. Sci. 2008, 53, 2359-2365.
68. Migliaccio, A.; Castoria, G.; Di Domenico, M.; Ciociola, A.; Lombardi, M.; De Falco, A.; Nanayakkara, M.; Bottero, D.; De Stasio, R.; Varricchio, L.; et al. Crosstalk between EGFR and extranuclear steroid receptors. Ann. NY Acad. Sci. 2006, 1089, 194-200.
69. Fiorelli, A.; Ricciardi, C.; Pannone, G.; Santoro, A.; Bufo, P.; Santini, M.; Serpico, R.; Rullo, R.; Pierantoni, G.M.; Di Domenico, M. Interplay between steroid receptors and neoplastic progression in sarcoma tumors. J. Cell. Physiol. 2011, doi: 10.1002/jcp.22645.
70. Miyamoto, S.; Teramoto, H.; Gutkind, J.S.; Yamada, K.M. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: Roles of integrin aggregation and occupancy of receptors. J. Cell. Biol. 1996, 135, 1633-1642.
71. Moro, L.; Venturino, M.; Bozzo, C.; Silengo, L.; Altruda, F.; Beguinot, L.; Tarone, G.; Defilippi, P. Integrins induce activation of EGF receptor: Role in MAP kinase induction and adhesion-dependent cell survival. EMBO J. 1998, 17, 6622-6632.
72. Wang, Z.; Wang, M.; Carr, B.I. Integrin alpha5-induced EGFR activation by prothrombin triggers hepatocyte apoptosis via the JNK signaling pathway. J. Cell. Physiol. 2008, 216, 551-557.
73. Liu, D.; Aguirre Ghiso, J.; Estrada, Y.; Ossowski, L. EGFR is a transducer of the uro kinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 2002, 1, 445-457.
74. Monaghan-Benson, E.; McKeown-Longo, P.J. Urokinase-type plasminogen activator receptor regulates a novel pathway of fibronectin matrix assembly requiring Src-dependent transactivation of epidermal growth factor receptor. J. Biol. Chem. 2006, 281, 9450-9459.
75. Zheng, Q.; Tang, Z.Y.; Xue, Q.; Shi, D.R.; Song, H.Y.; Tang, H.B. Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor. J. Cancer Res. Clin. Oncol. 2000, 126, 641-646.
76. Porcile, C.; Bajetto, A.; Barbieri, F.; Barbero, S.; Bonavia, R.; Biglieri, M.; Pirani, P.; Florio, T.; Schettini, G. Stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12) stimulates ovarian cancer cell growth through the EGF receptor transactivation. Exp. Cell Res. 2005, 308, 241-253.
77. 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, 1594-1600.
78. Wu, T. Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treat. Rev. 2006, 32, 28-44.
79. Han, C.; Michalopoulos, G.K.; Wu, T. Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J. Cell. Physiol. 2006, 207, 261-270.
80. Chen, Y.; Long, H.; Wu, Z.; Jiang, X.; Ma, L. EGF transregulates opioid receptors through EGFR-mediated GRK2 phosphorylation and activation. Mol. Biol. Cell. 2008, 19, 2973-2983.
81. Huang, Y.; Kim, S.O.; Jiang, J.; Frank, S.J. Growth hormone-induced phosphorylation of epidermal growth factor (EGF) receptor in 3T3-F442A cells. Modulation of EGF-induced trafficking and signaling. J. Biol. Chem. 2003, 278, 18902-18913.
82. Gonzalez, L.; Diaz, M.E.; Miquet, J.G.; Sotelo, A.I.; Fernandez, D.; Dominici, F.P.; Bartke, A.; Turyn, D. GH modulates hepatic epidermal growth factor signaling in the mouse. J. Endocrinol. 2010, 204, 299-309.
83. Garcia-Caballero, T.; Mertani, H.M.; Lambert, A.; Gallego, R.; Fraga, M.; Pintos, E.; Forteza, J.; Chevallier, M.; Lobie, P.E.; Vonderhaar, B.K.; et al. Increased expression of growth hormone and prolactin receptors in hepatocellular carcinomas. Endocrine 2000, 12, 265-271.
84. Gardner, O.S.; Dewar, B.J.; Earp, H.S.; Samet, J.M.; Graves, L.M. Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation. J. Biol. Chem. 2003, 278, 46261-46269.
85. Yu, J.; Shen, B.; Chu, E.S.; Teoh, N.; Cheung, K.F.; Wu, C.W.; Wang, S.; Lam, C.N.; Feng, H.; Zhao, J.; et al. Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro. Hepatology 2010, 51, 2008-2019.
86. Hsu, J.M.; Chen, C.T.; Chou, C.K.; Kuo, H.P.; Li, L.Y.; Lin, C.Y.; Lee, H.J.; Wang, Y.N.; Liu, M.; Liao, H.W.; et al. Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat. Cell. Biol. 2011, 13, 174-181.
87. Reinehr, R.; Haussinger, D. Epidermal growth factor receptor signaling in liver cell proliferation and apoptosis. Biol. Chem. 2009, 390, 1033-1037.
88. Maretzky, T.; Zhou, W.; Huang, X.Y.; Blobel, C.P. A transforming Src mutant increases the bioavailability of EGFR ligands via stimulation of the cell-surface metalloproteinase ADAM17. Oncogene 2011, 30, 611-618.
89. Ito, Y.; Kawakatsu, H.; Takeda, T.; Sakon, M.; Nagano, H.; Sakai, T.; Miyoshi, E.; Noda, K.; Tsujimoto, M.; Wakasa, K.; et al. Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype. J. Hepatol. 2001, 35, 68-73.
90. Lau, G.M.; Yu, G.L.; Gelman, I.H.; Gutowski, A.; Hangauer, D.; Fang, J.W. Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro. Dig. Dis. Sci. 2009, 54, 1465-1474.
91. Kyula, J.N.; Van Schaeybroeck, S.; Doherty, J.; Fenning, C.S.; Longley, D.B.; Johnston, P.G. Chemotherapy-induced activation of ADAM-17: A novel mechanism of drug resistance in colorectal cancer. Clin. Cancer Res. 2010, 16, 3378-3389.
92. Civenni, G.; Holbro, T.; Hynes, N.E. Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells. EMBO Rep. 2003, 4, 166-171.
93. Schafer, B.; Gschwind, A.; Ullrich, A. Multiple G-protein-coupled receptor signals converge n the epidermal growth factor receptor to promote migration and invasion. Oncogene 2004, 23, 991-999.
94. Shepard, H.M.; Brdlik, C.M.; Schreiber, H. Signal integration: A framework for understanding the efficacy of therapeutics targeting the human EGFR family. J. Clin. Invest. 2008, 118, 3574-3581.
95. Hu, T.; Li, C. Convergence between Wnt-beta-catenin and EGFR signaling in cancer. Mol. Cancer 2010, 9, 236.
96. Adams, T.E.; McKern, N.M.; Ward, C.W. Signalling by the type 1 insulin-like growth factor receptor: Interplay with the epidermal growth factor receptor. Growth Factors 2004, 22, 89-95.
97. van der Veeken, J.; Oliveira, S.; Schiffelers, R.M.; Storm, G.; Bergen En Henegouwen, P.M.; Roovers, R.C. Crosstalk between epidermal growth factor receptor- and insulin-like growth factor-1 receptor signaling: Implications for cancer therapy. Curr. Cancer Drug Targets 2009, 9, 748-760.
98. Wang, S.E.; Xiang, B.; Guix, M.; Olivares, M.G.; Parker, J.; Chung, C.H.; Pandiella, A.; Arteaga, C.L. Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol. Cell. Biol. 2008, 28, 5605-5620.
99. Murillo, M.M.; del Castillo, G.; Sanchez, A.; Fernandez, M.; Fabregat, I. Involvement of EGF receptor and c-Src in the survival signals induced by TGF-beta1 in hepatocytes. Oncogene 2005, 24, 4580-4587.
100. Matsuo, M.; Sakurai, H.; Ueno, Y.; Ohtani, O.; Saiki, I. Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin alphav-mediated ADAM activity in hepatocellular carcinoma: A novel functional target for gefitinib. Cancer Sci. 2006, 97, 155-162.
101. Koff J.L.; Shao, M.X.; Ueki, I.F.; Nadel, J.A. Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. Am. J. Physiol. Lung Cell Mol. Physiol. 2008, 294, L1068-1075.
102. Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J.F.; de Oliveira, A.C.; Santoro, A.; Raoul, J.L.; Forner, A.; et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008, 359, 378-390.
103. Villanueva, A.; Llovet, J.M. Targeted therapies for hepatocellular carcinoma. Gastroenterology 2011, submitted.
104. Kim, L.C.; Song, L.; Haura, E.B. Src kinases as therapeutic targets for cancer. Nat. Rev. Clin. Oncol. 2009, 6, 587-595.
105. Murumkar, P.R.; DasGupta, S.; Chandani, S.R.; Giridhar, R.; Yadav, M.R. Novel TACE inhibitors in drug discovery: A review of patented compounds. Exp. Opin. Ther. Pat. 2010, 20, 31-57.
106. Ishikawa, N.; Daigo, Y.; Takano, A.; Taniwaki, M.; Kato, T.; Hayama, S.; Murakami, H.; Takeshima, Y.; Inai, K.; Nishimura, H.; et al. Increases of amphiregulin and transforming growth factor-alpha in serum as predictors of poor response to gefitinib among patients with advanced non-small cell lung cancers. Cancer Res. 2005, 65, 9176-9184.
107. Daub, H.; Weiss, F.U.; Wallasch, C.; Ullrich, A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 1996, 379, 557-560.
108. Lappano, R.; Maggiolini, M. G protein-coupled receptors: Novel targets for drug discovery in cancer. Nat. Rev. Drug Discov 2011, 10, 47-60.
109. Kar, S.; Yousem, S.A.; Carr, B.I. Endothelin-1 expression by human hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 1995, 216, 514-519
110. Huang, F.; Geng, X.P. Chemokines and hepatocellular carcinoma. World J. Gastroenterol. 2010, 16, 1832-1836.
111. Wu, J.M.; Xu, Y.; Skill, N.J.; Sheng, H.; Zhao, Z.; Yu, M.; Saxena, R.; Maluccio, M.A. Autotaxin expression and its connection with the TNF-alpha-NF-kappaB axis in human hepatocellular carcinoma. Mol. Cancer 2010, 9, 71.
112. Jiang, G.; Xu, Y.; Fujiwara, Y.; Tsukahara, T.; Tsukahara, R.; Gajewiak, J.; Tigyi, G.; Prestwich, G.D. Alpha-substituted phosphonate analogues of lysophosphatidic acid (LPA) selectively inhibit production and action of LPA. ChemMedChem 2007, 2, 679-690