Drug development of MET inhibitors: targeting oncogene addiction and expedience (original) (raw)

• Trusolino, L. & Comoglio, P. M. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nature Rev. Cancer 2, 289–300 (2002).
  Article CAS Google Scholar
• Birchmeier, C., Birchmeier, W., Gherardi, E. & Vande Woude, G. F. Met, metastasis, motility and more. Nature Rev. Mol. Cell. Biol. 4, 915–925 (2003).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Zeng, Q. 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article Google Scholar
• Takayama, H., La Rochelle, W. J., Anver, M., Bockman, D. E. & Merlino, 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Schmidt, C. et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699–702 (1995).
  Article CAS PubMed Google Scholar
• Michalopoulos, G. K. & DeFrances, M. C. Liver regeneration. Science 276, 60–66 (1997).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Matsumoto, K. & Nakamura, T. Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases. Kidney Int. 59, 2023–2038 (2001).
  Article CAS PubMed Google Scholar
• Rabkin, R. et al. Hepatocyte growth factor receptor in acute tubular necrosis. J. Am. Soc. Nephrol. 12, 531–540 (2001).
  Article CAS PubMed Google Scholar
• Okada, H. & Kalluri, R. Cellular and molecular pathways that lead to progression and regression of renal fibrogenesis. Curr. Mol. Med. 5, 467–474 (2005).
  Article CAS PubMed Google Scholar
• Liu, Y. & Yang, J. Hepatocyte growth factor: new arsenal in the fights against renal fibrosis? Kidney Int. 70, 238–240 (2006).
  Article CAS PubMed Google Scholar
• Ueki, T. et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nature Med. 5, 226–230 (1999).
  Article CAS PubMed Google Scholar
• Watanabe, M. et al. Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis. Mol. Ther. 12, 58–67 (2005).
  Article CAS PubMed Google Scholar
• Boccaccio, C. & Comoglio, P. M. Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nature Rev. Cancer 6, 637–645 (2006).
  Article CAS Google Scholar
• Comoglio, P. M. & Trusolino, L. Invasive growth: from development to metastasis. J. Clin. Invest. 109, 857–862 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Danilkovitch-Miagkova, A. & Zbar, B. Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J. Clin. Invest. 109, 863–867 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Cooper, C. S. et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311, 29–33 (1984).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Boccaccio, C. et al. The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature 434, 396–400 (2005). First in vivo demonstration that lentiviral-mediated somatic transduction of oncogenic MET in hepatocytes of adult mice leads to the development of hepatocellular carcinomas.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• Kuniyasu, H. et al. Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem. Biophys. Res. Commun. 189, 227–232 (1992).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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). First in vivo demonstration that transgenic overexpression of wild-type MET in mouse hepatocytes leads to the development of hepatocellular carcinomas.
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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). First identification of naturally-occurring oncogenic mutations of MET in humans.
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Lee, J. H. et al. A novel germ line juxtamembrane MET mutation in human gastric cancer. Oncogene 19, 4947–4953 (2000).
  Article CAS PubMed Google Scholar
• 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). First report of a direct involvement of MET in tumour metastasis in humans. Neoplastic cells harbouring activating mutations of the MET gene undergo clonal expansion during the metastatic spreading of head and neck squamous-cell carcinomas.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Danilkovitch-Miagkova, A. & Zbar, B. Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J. Clin. Invest. 109, 863–867 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Michieli, P. et al. Mutant Met-mediated transformation is ligand-dependent and can be inhibited by HGF antagonists. Oncogene 18, 5221–5231 (1999).
  Article CAS PubMed Google Scholar
• Koochekpour, S. et al. Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res. 57, 5391–5398 (1997).
  CAS PubMed Google Scholar
• 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).
  CAS PubMed PubMed Central Google Scholar
• Ferracini, R. et al. Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas. Oncogene 12, 1697–1705 (1996).
  CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Takayama, H. et al. Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc. Natl Acad. Sci. USA 94, 701–706 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• Sharp, R. et al. Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis. Nature Med. 8, 1276–1280 (2002).
  Article CAS PubMed Google Scholar
• Kobayashi, T. et al. Hepatocyte growth factor specifically binds to sulfoglycolipids. J. Biol. Chem. 269, 9817–9821 (1994).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Mars, W. M., Zarnegar, R. & Michalopoulos, G. K. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. Am. J. Pathol. 143, 949–958 (1993).
  CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Lietha, D., Chirgadze, D. Y., Mulloy, B., Blundell, T. L. & Gherardi, E. Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor. EMBO J. 20, 5543–5555 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Matsumoto, K., Kataoka, H., Date, K. & Nakamura, T. Cooperative interaction between α- and β-chains of hepatocyte growth factor on c-Met receptor confers ligand-induced receptor tyrosine phosphorylation and multiple biological responses. J. Biol. Chem. 273, 22913–22920 (1998).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Trusolino L, Pugliese L, Comoglio PM . Interactions between scatter factors and their receptors: hints for therapeutic applications. FASEB J. 12, 1267–1280 (1998).
  Article CAS PubMed Google Scholar
• Chan, A. M. et al. Identification of a competitive HGF antagonist encoded by an alternative transcript. Science 254, 1382–1385 (1991).
  Article CAS PubMed Google Scholar
• Montesano, R. et al. Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis. Cell Growth Differ. 9, 355–365 (1998).
  CAS PubMed Google Scholar
• Matsumoto, K. & Nakamura, T. NK4 (HGF-antagonist/angiogenesis inhibitor) in cancer biology and therapeutics, Cancer Sci. 94, 321–327 (2003).
  Article CAS PubMed Google Scholar
• Matsumoto, K. & Nakamura, T. NK4 gene therapy targeting HGF-Met and angiogenesis. Front. Biosci. 13, 1943–1951 (2008).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Michieli, P. et al. Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 6, 61–73 (2004).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Registry of federally and privately supported clinical trials conducted in the United States [online]
• Martens, T. et al. A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin. Cancer Res. 12, 6144–6152 (2006).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Berthou, S. et al. The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants. Oncogene 23, 5387–5393 (2004).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article Google Scholar
• 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).
  Google Scholar
• 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).
  Google Scholar
• 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).
  Google Scholar
• 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).
  Google Scholar
• 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).
  Google Scholar
• 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).
  Google Scholar
• Conquering cancer with novel therapeutics. ArQule website [online]
• SuperGen reports dosing of first patient in Phase I trial of novel tyrosine kinase inhibitor. SuperGen website [online]
• 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).
  Google Scholar
• Perera, T. Selective inhibition of Met kinase: JNJ38877605. Spring CTEP Early Drug Development Meeting, Rockville, Maryland, USA (2007).
  Google Scholar
• Bertotti, A. & Comoglio, P. M. Tyrosine kinase signal specificity: lessons from the HGF receptor. Trends Biochem. Sci. 28, 527–533 (2003).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Boccaccio, C. et al. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature 391, 285–288 (1998).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• Sharma, S. V. & Settleman, J. Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev. 21, 3214–3231 (2007).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Pennacchietti, S. et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell. 3, 347–361 (2003).
  Article PubMed Google Scholar
• Bhowmick, N. A., Neilson, E. G. & Moses, H. L. Stromal fibroblasts in cancer initiation and progression. Nature 432, 332–337 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Steeg, P. S. Angiogenesis inhibitors: motivators of metastasis? Nature Med. 9, 822–823 (2003).
  Article CAS PubMed Google Scholar
• Bottaro, D. P. & Liotta, L. A. Cancer: Out of air is not out of action. Nature 423, 593–595 (2003).
  Article CAS PubMed Google Scholar
• 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).
  Article PubMed PubMed Central Google Scholar
• Abounader, R. et al. Regulation of c-Met-dependent gene expression by PTEN. Oncogene 23, 9173–9182 (2004).
  Article CAS PubMed Google Scholar
• Stommel, J. M. et al. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318, 287–290 (2007).
  Article CAS PubMed Google Scholar
• Engelman, J. A. et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039–1043 (2007). First description of MET gene amplification as a mechanism of acquired resistance to epidermal growth factor receptor inhibitors.
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190–1203 (2007).
  Article CAS PubMed Google Scholar
• Guo, A. et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl Acad. Sci. USA 105, 692–697 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Green, D. R. Even, G. I. A matter of life and death. Cancer Cell 1, 19–30 (2002).
  Article CAS PubMed Google Scholar
• Harrington, E. A., Fanidi, A. & Evan G. I. Oncogenes and cell death. Curr. Opin. Genet. Dev. 4, 120–129 (1994).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Rasola, A. et al. Hepatocyte growth factor sensitizes human ovarian carcinoma cell lines to paclitaxel and cisplatin. Cancer Res. 64, 1744–1750 (2004).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Giordano, S. et al. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nature Cell Biol. 4, 720–724 (2002).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Conrotto, P. et al. Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood 105, 4321–4329 (2005). References 123–130 provide information on how MET-dependent signals can be amplified and/or diversified by MET association with surface transmembrane partners, including CD44, β4 integrin and plexin B.
  Article CAS PubMed Google Scholar
• Di Renzo, M. F., et al. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7, 2549–2553 (1992).
  CAS PubMed Google Scholar
• Ruco, L., et al. D. Expression of Met protein in thyroid tumours. J. Pathol. 180, 266–270 (1996).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Di Renzo, M. F., et al. Overexpression of the Met/HGF receptor in ovarian cancer. Int. J. Cancer 58, 658–662 (1994).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Humphrey, P. A., et al. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am. J. Pathol. 147, 386–396 (1995).
  CAS PubMed PubMed Central Google Scholar
• Natali, P. G., et al. Overexpression of the met/HGF receptor in renal cell carcinomas. Int. J. Cancer 69, 212–217 (1996).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Wielenga, 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).
  Article CAS PubMed PubMed Central Google Scholar
• Morello, S., et al. MET receptor is overexpressed but not mutated in oral squamous cell carcinomas. J. Cell. Physiol. 189, 285–290 (2001).
  Article CAS PubMed Google Scholar
• Big biotechs take antibody approach to blocking Met receptor. Chemical & Engineering news [online]