Drug development of MET inhibitors: Targeting oncogene addiction and expedience

Nature Reviews Drug Discovery

Volumn 7, Issue 6, 2008, Pages 504-516

  Comoglio, Paolo M ^a   Giordano, Silvia ^a   Trusolino, Livio ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

3 [1 (2,6 DICHLORO 3 FLUOROPHENYL)ETHOXY] 5 [1 (4 PIPERIDINYL) 1H PYRAZOL 4 YL] 2 PYRIDINYLAMINE; 5 (2,6 DICHLOROBENZYLSULFONYL) 3 [3,5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1,3 DIHYDRO 2H INDOL 2 ONE; AMG 102; ANTINEOPLASTIC AGENT; ARQ 197; BIOLOGICAL PRODUCT; DOCETAXEL; ENZYME ANTIBODY; ENZYME INHIBITOR; JNJ 38877605; K 252; MET TYROSINE KINASE; MET TYROSINE KINASE INHIBITOR; MK 2461; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY L2G7; MONOCLONAL ANTIBODY OA 5D5; MP 470; N (3 CHLOROPHENYL) 3 [3,5 DIMETHYL 4 (4 METHYL 1 PIPERAZINYLCARBONYL) 1H PYRROL 2 YLMETHYLENE] 2,3 DIHYDRO N METHYL 2 OXO 1H INDOLE 5 SULFONAMIDE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT SCATTER FACTOR; SCATTER FACTOR; SCATTER FACTOR ANTIBODY; SCATTER FACTOR DERIVATIVE; SGX 523; TEMOZOLOMIDE; UNCLEAVABLE SCATTER FACTOR; UNINDEXED DRUG; XL 880;

ADVANCED CANCER; ANGIOGENESIS; APOPTOSIS; CANCER CELL CULTURE; CANCER GROWTH; CANCER INHIBITION; CARCINOGENESIS; CELL INVASION; CLINICAL TRIAL; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; GLIOBLASTOMA; HEAD AND NECK CANCER; HUMAN; KIDNEY CANCER; METASTASIS; NONHUMAN; ONCOGENE; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; STOMACH CANCER;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; GENE EXPRESSION REGULATION, NEOPLASTIC; HEPATOCYTE GROWTH FACTOR; HUMANS; MOLECULAR STRUCTURE; NEOPLASMS; ONCOGENES; PROTO-ONCOGENE PROTEINS C-MET;

EID: 44449151030     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2530     Document Type: Review

References (143)

1. Trusolino, L. & Comoglio, P. M. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nature Rev. Cancer 2, 289-300 (2002).
2. Birchmeier, C., Birchmeier, W., Gherardi, E. & Vande Woude, G. F. Met, metastasis, motility and more. Nature Rev. Mol. Cell. Biol. 4 915-925 (2003).
3. Xiao, G. H. et al. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc. Natl Acad. Sci. USA 98, 247-252 (2001).
4. Zeng, O. et al. Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NF-κB. J. Biol. Chem. 277, 25203-25208 (2002).
5. Bladt, F., Riethmacher, D., Isenmann, S., Aguzzi, A. & Birchmeier, C. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 376, 768-771 (1995).
6. Streit, A. et al. A role for HGF/SF in neural induction and its expression in Hensen's node during gastrulation. Development 121, 813-824 (1995).
7. Andermacher, E., Surani, M. A. & Gherardi, E. Co-expression of the HGF/SF and c-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev. Genet. 18, 254-266 (1996).
8. Takayama, H., La Rochelle, W. J., Anver, M., Bockman, D. E. & Mertino, G. Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development. Proc. Natl Acad. Sci. USA 93, 5866-5871 (1996).
9. Bussolino, F. et al. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J. Cell Biol. 119, 629-641 (1992).
10. Schmidt, C. et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699-702 (1995).
11. Michalopoulos, G. K. & DeFrances, M. C. Liver regeneration. Science 276, 60-66 (1997).
12. Nakamura, T., Mizuno, S., Matsumoto, K., Sawa, Y. & Matsuda, H. Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. J. Clin. Invest. 106, 1511-1519 (2000).
13. Matsumoto, K. & Nakamura, T. Hepatocyte growth factor: Renotropic role and potential therapeutics for renal diseases. Kidney Int. 59 2023-2038 (2001).
14. Rabkin, R. et al. Hepatocyte growth factor receptor in acute tubular necrosis. J. Am. Soc. Nephrol. 12, 531-540 (2001).
15. Okada, H. & Kalluri, R. Cellular and molecular pathways that lead to progression and regression of renal fibrogenesis. Curr. Mol. Med. 5, 467-474 (2005).
16. Liu, Y. & Yang, J. Hepatocyte growth factor: New arsenal in the fights against renal fibrosis? Kidney Int. 70, 238-240 (2006).
17. Ueki, T. et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nature Med. 5, 226-230 (1999).
18. Watanabe, M. et al. Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis. Mol. Ther. 12, 58-67 (2005).
19. Boccaccio, C. & Comoglio, P. M. Invasive growth: A MET-driven genetic programme for cancer and stem cells. Nature Rev. Cancer 6, 637-645 (2006).
20. Comoglio, P. M. & Trusolino, L. Invasive growth: From development to metastasis. J. Clin. Invest. 109, 857-862 (2002).
21. Danilkovitch-Miagkova, A. & Zbar, B. Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J. Clin. Invest. 109, 863-867 (2002).
22. Cooper, C. S. et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311, 29-33 (1984).
23. Liang, T. J., Reid, A. E., Xavier, R., Cardiff, R. D. & Wang, T. C. Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. J. Clin. Invest. 97, 2872-2877 (1996).
24. Boccaccio, C. et al. The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature 434, 396-400 (2005).
25. Soman, N. R., Correa, P., Ruiz, B. A. & Wogan, G. N. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc. Natl Acad. Sci. USA 88 4892-4896 (1991).
26. Houldsworth, J., Cordon-Cardo, C., Ladanyi, M., Kelsen, D. P. & Chaganti, R. S. Gene amplification in gastric and esophageal adenocarcinomas. Cancer Res. 50, 6417-6422 (1990).
27. Kuniyasu, H. et al. Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem. Biophys. Res. Commun. 189, 227-232 (1992).
28. Hara, T. et al. Amplification of c-myc, K-sam, and c-met in gastric cancers: Detection by fluorescence in situ hybridization. Lab. Invest. 78, 1143-1153 (1998).
29. Miller, C. T. et al. Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma. Oncogene 25, 409-418 (2006).
30. Bean, J. et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl Acad. Sci. USA 104, 20932-20937 (2007).
31. Tong, C. Y. et al. Detection of oncogene amplifications in medulloblastomas by comparative genomic hybridization and array-based comparative genomic hybridization. J. Neurosurg. 100, 187-193 (2004).
32. Wang, R., Ferrell, L. D., Faouzi, S., Maher, J. J. & Bishop, J. M. Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J. Cell Biol. 153 1023-1034 (2001).
33. Di Renzo, M. F. et al. Overexpression and amplification of the MET/HGF receptor gene during the progression of colorectal cancer. Clin. Cancer Res. 1, 147-154 (1995).
34. Schmidt, L. et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nature Genet. 16, 68-73 (1997).
35. Park, W. S. et al. Somatic mutations in the kinase domain of the MET/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 59, 307-310 (1999).
36. Lee, J. H. et al. A novel germ line juxtamembrane MET mutation in human gastric cancer. Oncogene 19, 4947-4953 (2000).
37. Di Renzo, M. F. et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 19, 1547-1555 (2000).
38. Graveel, C. et al. Activating Met mutations produce unique tumor profiles in mice with selective duplication of the mutant allele. Proc. Natl Acad. Sci. USA 101, 17198-17203 (2004).
39. Danilkovitch-Miagkova, A. & Zbar, B. Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J. Clin. Invest. 109, 863-867 (2002).
40. Boccaccio, C., Gaudino, G., Gambarotta, G., Galimi, F. & Comoglio, P. M. Hepatocyte growth factor (HGF) receptor expression is inducible and is part of the delayed-early response to HGF. J. Biol. Chem. 269 12846-12851 (1994).
41. Aguirre Ghiso, J. A., Alonso, D. F., Farias, E. F., Gomez, D. E. & de Kier Joffe, E. B. Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Eur. J. Biochem. 263, 295-304 (1999).
42. Parr, C., Watkins, G., Mansel, R. E. & Jiang, W. G. The hepatocyte growth factor regulatory factors in human breast cancer. Clin. Cancer Res. 10, 202-211 (2004).
43. Michieli, P. et al. Mutant Met-mediated transformation is ligand-dependent and can be inhibited by HGF antagonists. Oncogene 18, 5221-5231 (1999).
44. Koochekpour, S. et al. Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res. 57, 5391-5398 (1997).
45. Tuck, A. B., Park, M., Sterns, E. E., Boag, A. & Elliott. B. E. Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. Am. J. Pathol. 148, 225-232 (1996).
46. Ferracini, R. et al. Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas. Oncogene 12, 1697-1705 (1996).
47. Ferracini, R. et al. The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 10, 739-749 (1995).
48. Rong, S., Segal, S., Anver, M., Resau, J. H. & Vande Woude, G. F. Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc. Natl Acad. Sci. USA 91, 4731-4735 (1994).
49. Bellusci, S. et al. Creation of an hepatocyte growth factor/ scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity. Oncogene 9 1091-1099 (1994).
50. Jeffers, M., Rong, S., Anver, M. & Vande Woude, G. F. Autocrine hepatocyte growth factor/scatter factor signalling induces transformation and the invasive/metastatic phenotype in C127 cells. Oncogene 13, 853-861 (1996).
51. Takayama, H. et al. Diverse tumorigenesis associated with aberrant development in mice oyerexpressing hepatocyte growth factor/scatter factor. Proc. Natl Acad. Sci. USA 94, 701-706 (1997).
52. Otsuka, T. et al. c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype. Cancer Res. 58, 5157-5167 (1998).
53. Sharp, R. et al. Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis. Nature Med. 8, 1276-1280 (2002).
54. Kobayashi, T. et al. Hepatocyte growth factor specifically binds to sulfoglycolipids. J. Biol. Chem. 269, 9817-9821 (1994).
55. Lyon, M., Deakin, J. A., Mizuno, K, Nakamura, T. & Gallagher. J. T. Interaction of hepatocyte growth factor with heparan-sulfate. Elucidation of the major heparan sulfate structural determinants. J. Biol. Chem. 269, 11216-11223 (1994).
56. Naldini, L. et al. Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J. 11, 4825-4833 (1992).
57. Mars, W. M., Zarnegar, R. & Michalopoulos, G. K. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. Am. J. Pothol. 143, 949-958 (1993).
58. Lokker, N. A. et al. Structure-function analysis of hepatocyte growth factor: Identification of variants that lack mitogenic activity yet retain high affinity receptor binding. EMBO J. 11. 2503-2510 (1992).
59. Lietha, D., Chirgadze, D. Y., Mulloy, B, Blundell, T. L. & Gherardi, E. Crystal structures of NK 1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor. EMBO J. 20, 5543-5555 (2001).
60. Matsumoto, K., Kataoka, H., Date K. & Nakamura, T. Cooperative interaction between α- and β-chains of hepatocyte growth factor an c-Met receptor confers ligand-induced receptor tyrosine phosphorylation and multiple biological responses. J. Biol. Chem. 273, 22913-22920 (1998).
61. Stamos J., Lazarus, R. A., Yao, X, Kirchhofer, D. & Wiesmann, C. Crystal structure of the HGF β-chain in complex with the Sema domain of the Met receptor EMBO J. 23, 2325-2335 (2004).
62. Kirchhofer, D. et al. Structural and functional basis of the serine protease-like HGF beta-chain in Met binding and signaling, J. Biol. Chem. 279, 39915-39924 (2004).
63. Trusolino L., Pugliese L., Comoglio PM. Interactions between scatter factors and their receptors: Hints for therapeutic applications. FASEB J. 12, 1267-1280 (1998).
64. Chan, A. M. et al. Identification of a competitive HGF antagonist encoded by an alternative transcript Science 254, 1382-1385 (1991).
65. Montesano, R. et al. Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis. Cell Growth Differ. 9, 355-365 (1998).
66. Matsumoto, K. & Nakamura, T. NK4 (HGF=antagonist/angiogenesis inhibitor) in cancer biology and therapeutics, Cancer Sci. 94 321-327 (2003).
67. Matsumoto, K. & Nakamura, T. NK4 gene therapy targeting HGF-Met and angiogenesis. Front. Biosci. 13, 1943-1951 (2008).
68. Kuba, K. et al. HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice. Cancer Res. 60, 6737-6743 (2000).
69. Mazzone, M. et al. An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice. J. Clin. Invest. 114, 1418-1432 (2004).
70. Michieli, P. et al. Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 6, 61-73 (2004).
71. Kong-Beltran, M., Stamos, J. & Wickramasinghe, D. The Sema domain of Met is necessary for receptor dimerization and activation. Cancer Cell 6, 75-84 (2004).
72. Burgess, T. et al. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Res. 66, 1721-1729 (2006).
73. Kim, K. J. et al. Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. Clin. Cancer Res. 12, 1292-1298 (2006).
74. Jun, H. T. et al. AMG 102, a fully human anti-hepatocyte growth factor/scatter factor neutralizing antibody, enhances the efficacy of temozolomide or docetaxel in U-87 MG cells and xenografts. Clin. Cancer Res. 13, 6735-6742 (2007).
75. Registry of federally and privately supported clinical trials conducted in the United States [online]
76. Martens, T, et al. A novel one-armed anti-c-Met antibody inhibits glioblastorna growth in vivo. Clin. Cancer Res. 12, 6144-6152 (2006).
77. Petrelli, A. et al. Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity. Proc. Natl Acad. Sci. USA 103, 5090-5095 (2006).
78. Morotti, A., Mila, S., Accornero, P., Tagliabue, E. & Ponzetto, C. K252a inhibits the oncogenic properties of Met, the HGF receptor. Oncogene 21, 4885-4893 (2002).
79. Sattler M. et al. A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer Res. 63, 5462-5469 (2003).
80. Christensen, J. G. et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res 63, 7345-7355 (2003).
81. Berthou, S. et al. The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants. Oncogene 23, 5387-5393 (2004).
82. Smolen, G. A. et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc. Natl Acad. Sci. USA 103, 2316-2321 (2006).
83. Zou, H. Y. et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 67 4408-4417 (2007).
84. Eder, J. P. et al. Phase I experience with c-MET inhibitor XL880 administered orally to patients (pts) with solid tumors. J. Clin. Oncol. 25, 3526 (2007).
85. Ross, R. W. et al. A phase 2 study of the dual MET/VEGFR2 inhibitor XL880 in patients with papillary renal carcinoma. Abstract B249. AACR-NCI-EORTC: Molecular Targets and Cancer Therapeutics, San Francisco, California, USA (2007).
86. Jeay, S. et al. ARQ197, a highly selective small molecule inhibitor of c-Met, with selective antitumor properties in a broad spectrum of human cancer cells. Abstract 2369. AACR Annual Meeting, Los Angeles, California, USA (2007).
87. Munshi, N. et al. ARQ197, a highly selective inhibitor of c-Met, inhibits invasive and metastatic growth of cancer cells. Abstract 2367. AACR Annual Meeting. Los Angeles California, USA (2007).
88. Youzhi, L. I. et al. Anti-metastatic activity of ARQ197, a highly selective oral small molecule inhibitor of c-Met, in experimental metastatic models of colon cancer. Abstract 2191. AACR Annual Meeting, Los Angeles, California, USA (2007).
89. Youzhi, L. I. et al. Broad spectrum anti-cancer activity of ARQ197, a highly selective oral c-Met inhibitor, in multiple xenograft models. Abstract 2216. AACR Annual Meeting, Los Angeles, California, USA (2007).
90. Garcia, A. et al. Phase 1 study of ARQ 197, a selective inhibitor of the c-Met RTK in patients with metastatic solid tumors reaches recommended phase 2 dose. Abstract 3525. ASCO Annual Meeting, Chicago, Illinois, USA (2007).
91. Conquering cancer with novel therapeutics. ArQule website [online]
92. SuperGen reports dosing of first patient in Phase I trial of novel tyrosine kinase inhibitor, SuperGen website [online]
93. Froning, K. J. et al. SGX523: A potent and highly selective small molecule inhibitor of the MET receptor tyrosine kinase. Abstract 2366. AACR Annual Meeting, Los Angeles, California, USA (2007).
94. Perera, T. Selective inhibition of Met kinase: JNJ38877605. Spring CTEP Early Drug Development Meeting, Rockville, Maryland, USA (2007).
95. Bertotti, A. & Comogilo, P. M. Tyrosine kinase signal specificity: lessons from the HGF receptor. Trends Biochem. Sci. 28, 527-533 (2003).
96. Matzke, A., Herrlich, P., Ponta, H. & Orian-Rousseau, V. A five-amino-acid peptide blocks Met- and Ron-dependent cell migration. Cancer Res. 65, 6105-6110 (2005).
97. Atabey N. et al. Potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion and branching morphogenesis by antagonists of Grb2 Src homology 2 domain interactions. J. Biol. Chem. 276, 14308-14314 (2001).
98. Boccaccio, C. et al. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature 391, 285-288 (1998).
99. Sharma, S. V., Bell, D. W., Settleman, J. & Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nature Rev. Cancer 7, 169-181 (2007).
100. Sharma, S. V. & Settleman, J. Oncogene addiction: Setting the stage for molecularly targeted cancer therapy. Genes Dev. 21, 3214-3231 (2007).
101. Lutterbach, B. et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res. 67, 2081-2088 (2007).
102. Ivan, M., Bond, J. A., Prat, M., Comoglio, P. M. & Winford-Thomas, D. Activated ras and ret oncogenes induce over-expression of c-met (hepatocyte growth factor receptor) in human thyroid epithelial cells. Oncogene 14, 2417-2423 (1997).
103. Pennacchietti, S. et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell. 3, 347-361 (2003).
104. Bhowmick, N. A., Neilson, E. G. & Moses, H. L. Stromal fibroblasts in cancer initiation and progression. Nature 432, 332-337 (2004).
105. Kmiecik, T. E., Keller, J. R., Rosen, E. & Vande Woude, G. F. Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells. Blood 80, 2454-2457 (1992).
106. Steeg, P. S. Angiogenesis inhibitors: Motivators of metastasis? Nature Med. 9, 822-823 (2003).
107. Bottaro, D. P. & Liotta, L. A. Cancer: Out of air is not out of action. Nature 423, 593-595 (2003).
108. Amit, I., Wides, R. & Yarden, Y. Evolvable signaling networks of receptor tyrosine kinases: Relevance of robustness to malignancy and to cancer therapy. Mol. Syst. Biol. 3, 151 (2007).
109. Abounader, R. et al. Regulation of c-Met-dependent gene expression by PTEN. Oncogene 23, 9173-9182 (2004).
110. Stommel, J. M. et al. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318, 287-290 (2007).
111. Engelman, J. A. et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043 (2007).
112. Kaposi-Novak, P. et al. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype. J. Clin. Invest. 116, 1582-1595 (2006).
113. Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190-1203 (2007).
114. Guo, A. et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl Acad. Sci. USA 105, 692-697 (2008).
115. Green, D. R. Even, G. I. A matter of life and death. Cancer Cell 1, 19-30 (2002).
116. Harrington, E. A., Fanidi, A. & Evan G. I. Oncogenes and cell death. Curr. Opin. Genet. Dev. 4, 120-129 (1994).
117. Tikhomirov, O. & Carpenter, G. Ligand-induced, p38-dependent apoptosis in cells expressing high levels of epidermal growth factor receptor and ErbB-2. J. Biol. Chem. 279, 12988-12996 (2004).
118. Shima, N. et al. Tumor cytotoxic factor/hepatocyte growth factor from human fibroblasts: Cloning of its cDNA, purification and characterization of recombinant protein. Biochem. Biophys. Res. Commun. 180, 1151-1158 (1991).
119. Matteucci, E., Castoldi, R. & Desiderio, M. A. Hepatocyte growth factor induces pro-apoptotic genes in HepG2 hepatoma but not in B16-F1 melanoma cells. J. Cell. Physiol. 186, 387-396 (2001).
120. Rasola, A. et al. Hepatocyte growth factor sensitizes human ovarian carcinoma cell lines to paclitaxel and cisplatin. Cancer Res. 64, 1744-1750 (2004).
121. Coltella, N. et al. p38 MAPK turns hepatocyte growth factor to a death signal that commits ovarian cancer cells to chemotherapy-induced apoptosis. Int. J. Cancer 118, 2981-2990 (2006).
122. Michieli, P. et al. An HGF-MSP chimera disassociates the trophic properties of scatter factors from their pro-invasive activity. Nature Biotechnol. 20, 488-495 (2002).
123. Orian-Rousseau, V., Chen, L., Sleeman, J. P., Herrlich, P. & Ponta, H. CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev. 16, 3074-3086 (2002).
124. Orian-Rousseau, V. et al. Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin. Mol. Biol. Cell 18, 76-83 (2007).
125. Trusolino, L., Bertotti, A. & Comoglio, P. M. A signaling adapter function for α6β4 integrin in the control of HGF-dependent invasive growth. Cell 107, 643-654 (2001).
126. Bertotti, A., Comoglio, P. M. & Trusolino, L. β4 integrin is a transforming molecule that unleashes Met tyrosine kinase tumorigenesis. Cancer Res. 65, 10674-10679 (2005).
127. Bertotti, A., Comoglio, P. M. & Trusolino, L. β4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth. J Cell Biol. 175, 993-1003 (2006).
128. Giordano, S. et al. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nature Cell Biol. 4, 720-724 (2002).
129. Conrotto, P., Corso, S., Gamberini, S., Comoglio, P. M. & Giordano, S. Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene 23, 5131-5137 (2004).
130. Conrotto, P. et al. Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood 105, 4321-4329 (2005).
131. Di Renzo, M. F., et al. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7, 2549-2553 (1992).
132. Ruco, L, et al. D. Expression of Met protein in thyroid tumours. J. Pathol. 180, 266-270 (1996).
133. Chen, B. K., et al. Overexpression of c-Met protein in human thyroid tumors correlated with lymph node metastasis and clinicopathologic state. Pathol. Res. Pract. 195, 427-433 (1999).
134. Di Renzo, M. F., et al. Overexpression of the Met/HGF receptor in ovarian cancer. Int. J. Cancer 58, 658-662 (1994).
135. Di Renzo, M. F., Poulsom, R., Olivero, M., Comoglio, P. M. & Lemoine, N. R. Expression of the Met/hepatocyte growth factor receptor in human pancreatic cancer. Cancer Res. 55, 1129-1138 (1995).
136. Humphrey, P. A., et al. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am. J. Pathol. 147, 386-396 (1995).
137. Natali, P. G., et al. Overexpression of the met/HGF receptor in renal cell carcinomas. Int. J. Cancer 69, 212-217 (1996).
138. Ueki, T., Fujimoto. J., Suzuki, T., Yamamoto, H & Okamoto, E. Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma. Hepatology 25, 619-623 (1997).
139. Tavian, D., et al. U-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor mRNA is down-regulated in human hepatocellular carcinoma. Int. J. Cancer 87, 644-649 (2000).
140. Camp, R. L., Rimm, E. B. & Rimm, D. L. Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma. Cancer 86, 2259-2265 (1999).
141. Welenga, V. J., et al. Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal cancer. Am. J. Pathol. 157, 1563-1573 (2000).
142. Morello, S., et al. MET re-ceptor is overexpressed but not mutated in oral squamous cell carcinomas. J. Cell. Physiol. 189, 285-290 (2001).
143. Big biotechs take antibody approach to blocking Met receptor. Chemical & Engineering news [online]