Targeting MET in cancer: rationale and progress
Tóm tắt
Từ khóa
Tài liệu tham khảo
Cooper, C. S. et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311, 29–33 (1984).
Park, M. et al. Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc. Natl Acad. Sci. USA 84, 6379–6383 (1987). References 1 and 2 report a new transforming gene ( MET ) from a human osteogenic sarcoma cell line treated with N -methyl-N′-nitronitrosoguanidine. Subsequent work established that it is the fusion of regulatory sequences from chromosome 1 ( TPR ) and sequences from chromosome 7 encoding a receptor tyrosine kinase (MET).
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). Reference 3 shows that cells made autocrine for HGF/SF–MET expression become highly metastatic in immunocompromised mice.
Miyazawa, K. et al. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem. Biophys. Res. Commun. 163, 967–973 (1989).
Nakamura, T., Nawa, K., Ichihara, A., Kaise, N. & Nishino, T. Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett. 224, 311–316 (1987).
Nakamura, T. et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 342, 440–443 (1989).
Zarnegar, R. & Michalopoulos, G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res. 49, 3314–3320 (1989). References 4–7 describe the isolation, cloning and sequencing of a potent mitogen for rat hepatocyte cultures (HGF). Reference 6 further describes the sequence similarity between HGF and plasminogen.
Stoker, M., Gherardi, E., Perryman, M. & Gray, J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 327, 239–242 (1987).
Gherardi, E., Gray, J., Stoker, M., Perryman, M. & Furlong, R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc. Natl Acad. Sci. USA 86, 5844–5848 (1989). References 8 and 9 describe the discovery and characterization of a fibroblast-derived protein that causes dispersion of epithelial colonies (scatter factor). The reports establish a paracrine mechanism of action and describe changes in epithelial cells in culture that have now become known as EMT.
Weidner, K. M. et al. Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc. Natl Acad. Sci. USA 88, 7001–7005 (1991).
Bottaro, D. P. et al. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251, 802–804 (1991). A molecular biological and biochemical study establishes that MET is the receptor for HGF/SF.
Schmidt, C. et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699–702 (1995).
Uehara, Y. et al. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373, 702–705 (1995).
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). References 13–15 define the roles of HGF/SF and MET in mouse development through genetic experiments. References 13 and 14 demonstrate roles in survival and differentiation of epithelial cells of the liver and placenta. Reference 15 reports that MET is essential for EMT of the ventral dermomyotome and migration of myogenic precursor cells into the limbs, tongue and other organs.
Birchmeier, C., Birchmeier, W., Gherardi, E. & Vande Woude, G. F. Met, metastasis, motility and more. Nature Rev. Mol. Cell Biol. 4, 915–925 (2003).
Weidner, K. M. et al. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 384, 173–176 (1996). This report characterizes GAB1 as a universal docking protein of MET.
Lai, A. Z., Abella, J. V. & Park, M. Crosstalk in Met receptor oncogenesis. Trends Cell Biol. 19, 542–551 (2009).
Trusolino, L., Bertotti, A. & Comoglio, P. M. MET signalling: principles and functions in development, organ regeneration and cancer. Nature Rev. Mol. Cell Biol. 11, 834–848 (2010).
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). This is the first report of missense mutations in MET in patients with hereditary papillary renal carcinoma and in certain non-familial forms of renal cancer.
Schiering, N. et al. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a. Proc. Natl Acad. Sci. USA 100, 12654–12659 (2003).
Gherardi, E. et al. Structural basis of hepatocyte growth factor/scatter factor and MET signalling. Proc. Natl Acad. Sci. USA 103, 4046–4051 (2006). Reference 21 describes the first crystal structures of the kinase domain of MET. The report describes both the apo structure, as well as the structure of the kinase domain in complex with the inhibitor K-252A. Reference 22 describes Cryo-EM and SAXS structures of HGF/SF–MET complexes.
Kirchhofer, D. et al. Structural and functional basis of the serine protease-like hepatocyte growth factor β-chain in Met binding and signaling. J. Biol. Chem. 279, 39915–39924 (2004).
Owen, K. A. et al. Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA. Biochem. J. 426, 219–228 (2010).
Shimomura, T. et al. Activation of the zymogen of hepatocyte growth factor activator by thrombin. J. Biol. Chem. 268, 22927–22932 (1993).
Shimomura, T. et al. Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor. J. Biol. Chem. 272, 6370–6376 (1997).
Kawaguchi, T. et al. Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor. J. Biol. Chem. 272, 27558–27564 (1997).
List, K. et al. Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. Genes Dev. 19, 1934–1950 (2005).
Klezovitch, O. et al. Hepsin promotes prostate cancer progression and metastasis. Cancer Cell 6, 185–195 (2004).
Morris, M. R. et al. Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma. Cancer Res. 65, 4598–4606 (2005).
Chirgadze, D. Y. et al. Crystal structure of the NK1 fragment of HGF/SF suggests a novel mode for growth factor dimerization and receptor binding. Nature Struct. Biol. 6, 72–79 (1999).
Ultsch, M., Lokker, N. A., Godowski, P. J. & de Vos, A. M. Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution. Structure 6, 1383–1393 (1998).
Tolbert, W. D., Daugherty-Holtrop, J., Gherardi, E., Vande Woude, G. & Xu, H. E. Structural basis for agonism and antagonism of hepatocyte growth factor. Proc. Natl Acad. Sci. USA 107, 13264–13269 (2010). References 31 and 32 are the first reports of the crystal structure of the NK1 fragment of HGF/SF. An identical head-to-tail dimer is described in two different crystal forms. Reference 33 provides the first crystal structure of NK2, the product of the major HGF/SF splice variant.
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).
Niemann, H. H. et al. Structure of the human receptor tyrosine kinase met in complex with the listeria invasion protein InlB. Cell 130, 235–246 (2007). References 34 and 35 report on the first two crystal structures of fragments of the MET ectodomain in complex with the SPH domain of HGF/SF (reference 34) or the bacterial protein InlB (reference 35).
Ferraris, D. M., Gherardi, E., Di, Y., Heinz, D. W. & Niemann, H. H. Ligand-mediated dimerization of the Met receptor tyrosine kinase by the bacterial invasion protein InlB. J. Mol. Biol. 395, 522–532 (2010).
Ponzetto, C. et al. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77, 261–271 (1994). This report describes the bidentate docking site of MET (Y1349 and Y1356), which is essential in MET signalling and binds various adaptor molecules.
Maroun, C. R., Naujokas, M. A., Holgado-Madruga, M., Wong, A. J. & Park, M. The tyrosine phosphatase SHP-2 is required for sustained activation of extracellular signal-regulated kinase and epithelial morphogenesis downstream from the met receptor tyrosine kinase. Mol. Cell. Biol. 20, 8513–8525 (2000).
Paliouras, G. N., Naujokas, M. A. & Park, M. Pak4, a novel Gab1 binding partner, modulates cell migration and invasion by the Met receptor. Mol. Cell. Biol. 29, 3018–3032 (2009).
Schaeper, U. et al. Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J. Cell Biol. 149, 1419–1432 (2000).
Schaeper, U. et al. Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Proc. Natl Acad. Sci. USA 104, 15376–15381 (2007). References 40 and 41 describe the involvement of the tyrosine phosphatase SHP2 in downstream signalling of MET.
Grossmann, K. S., Rosario, M., Birchmeier, C. & Birchmeier, W. The tyrosine phosphatase Shp2 in development and cancer. Adv. Cancer Res. 106, 53–89 (2010).
Ishibe, S. et al. Met and the epidermal growth factor receptor act cooperatively to regulate final nephron number and maintain collecting duct morphology. Development 136, 337–345 (2009).
Montesano, R., Matsumoto, K., Nakamura, T. & Orci, L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 67, 901–908 (1991).
Woolf, A. S. et al. Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros. J. Cell Biol. 128, 171–184 (1995).
Mosesson, Y., Mills, G. B. & Yarden, Y. Derailed endocytosis: an emerging feature of cancer. Nature Rev. Cancer 8, 835–850 (2008).
Joffre, C. et al. A direct role for Met endocytosis in tumorigenesis. Nature Cell Biol. 13, 827–837 (2011). This report describes binding of the E3-ubiquitin ligase CBL to the juxtamembrane region of MET leading to downregulation of the receptor.
Peschard, P. et al. Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein. Mol. Cell 8, 995–1004 (2001).
Hammond, D. E., Urbe, S., Vande Woude, G. F. & Clague, M. J. Down-regulation of MET, the receptor for hepatocyte growth factor. Oncogene 20, 2761–2770 (2001).
Petrelli, A. et al. The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 416, 187–190 (2002).
Abella, J. V. et al. Met/Hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Mol. Cell. Biol. 25, 9632–9645 (2005).
Lee, J. H. et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19, 4947–4953 (2000).
Asaoka, Y. et al. Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion. Biochem. Biophys. Res. Commun. 394, 1042–1046 (2010).
Foveau, B. et al. Down-regulation of the met receptor tyrosine kinase by presenilin-dependent regulated intramembrane proteolysis. Mol. Biol. Cell 20, 2495–2507 (2009).
Dietrich, S. et al. The role of SF/HGF and c-Met in the development of skeletal muscle. Development 126, 1621–1629 (1999).
Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315, 1650–1659 (1986).
Borowiak, M. et al. Met provides essential signals for liver regeneration. Proc. Natl Acad. Sci. USA 101, 10608–10613 (2004).
Huh, C. G. et al. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc. Natl Acad. Sci. USA 101, 4477–4482 (2004).
Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. & Birchmeier, W. β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533–545 (2001). References 56, 57 and 60 describe an essential role of MET in liver regeneration and skin wound healing.
Snippert, H. J. et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327, 1385–1389 (2010).
Chmielowiec, J. et al. c-Met is essential for wound healing in the skin. J. Cell Biol. 177, 151–162 (2007).
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).
Ma, P. C. et al. Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer 47, 1025–1037 (2008).
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).
Ponzo, M. G. et al. Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. Proc. Natl Acad. Sci. USA 106, 12903–12908 (2009).
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).
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).
Kuniyasu, H. et al. Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem. Biophys. Res. Commun. 189, 227–232 (1992).
Rege-Cambrin, G. et al. Karyotypic analysis of gastric carcinoma cell lines carrying an amplified c-met oncogene. Cancer Genet. Cytogenet. 64, 170–173 (1992).
Knudsen, B. S. & Vande Woude, G. Showering c-MET-dependent cancers with drugs. Curr. Opin. Genet. Dev. 18, 87–96 (2008).
Bauer, T. W. et al. Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells. Mol. Cancer Ther. 5, 1676–1682 (2006).
Khoury, H. et al. HGF converts ErbB2/Neu epithelial morphogenesis to cell invasion. Mol. Biol. Cell 16, 550–561 (2005).
Yamamoto, N., Mammadova, G., Song, R. X., Fukami, Y. & Sato, K. Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells. J. Cell Sci. 119, 4623–4633 (2006).
Engelman, J. A. et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039–1043 (2007). The first report that cancer cells from patients with NSCLC acquire resistance to EGFR inhibitors through MET and ERBB3 signalling, and that combinations of EGFR and MET inhibitors can restore the suppression of cell growth.
Turke, A. B. et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 17, 77–88 (2010).
Zhang, Y. W. et al. MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth. Cancer Res. 70, 6880–6890 (2010).
Giordano, S. et al. The semaphorin 4D receptor controls invasive growth by coupling with Met. Nature Cell Biol. 4, 720–724 (2002).
Swiercz, J. M., Worzfeld, T. & Offermanns, S. Semaphorin 4D signaling requires the recruitment of phospholipase C γ into the plexin-B1 receptor complex. Mol. Cell. Biol. 29, 6321–6334 (2009).
Klaus, A. & Birchmeier, W. Wnt signalling and its impact on development and cancer. Nature Rev. Cancer 8, 387–398 (2008).
Boon, E. M., van der Neut, R., van de Wetering, M., Clevers, H. & Pals, S. T. Wnt signaling regulates expression of the receptor tyrosine kinase met in colorectal cancer. Cancer Res. 62, 5126–5128 (2002).
Liu, Y. et al. Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis. Development 136, 843–853 (2009).
Monga, S. P. et al. Hepatocyte growth factor induces Wnt-independent nuclear translocation of β-catenin after Met-β-catenin dissociation in hepatocytes. Cancer Res. 62, 2064–2071 (2002).
Brembeck, F. H. et al. Essential role of BCL9–2 in the switch between β-catenin's adhesive and transcriptional functions. Genes Dev. 18, 2225–2230 (2004).
Bhowmick, N. A. et al. TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303, 848–851 (2004).
Sridhar, S. C. & Miranti, C. K. Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases. Oncogene 25, 2367–2378 (2006).
Takahashi, M., Sugiura, T., Abe, M., Ishii, K. & Shirasuna, K. Regulation of c-Met signaling by the tetraspanin KAI-1/CD82 affects cancer cell migration. Int. J. Cancer 121, 1919–1929 (2007).
Sharp, R. et al. Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis. Nature Med. 8, 1276–1280 (2002).
Abounader, R. & Laterra, J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 7, 436–451 (2005).
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).
Grant, D. S. et al. Scatter factor induces blood vessel formation in vivo. Proc. Natl Acad. Sci. USA 90, 1937–1941 (1993).
Zhang, Y. W., Su, Y., Volpert, O. V. & Vande Woude, G. F. Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc. Natl Acad. Sci. USA 100, 12718–12723 (2003).
Sulpice, E. et al. Cross-talk between the VEGF-A and HGF signalling pathways in endothelial cells. Biol. Cell 101, 525–539 (2009).
Puri, N. et al. A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res. 67, 3529–3534 (2007).
Cantelmo, A. R. et al. Cell delivery of Met docking site peptides inhibit angiogenesis and vascular tumor growth. Oncogene 29, 5286–5298 (2010).
Hara, S. et al. Hypoxia enhances c-Met/HGF receptor expression and signaling by activating HIF-1α in human salivary gland cancer cells. Oral Oncol. 42, 593–598 (2006).
Ide, T. et al. Tumor-stromal cell interaction under hypoxia increases the invasiveness of pancreatic cancer cells through the hepatocyte growth factor/c-Met pathway. Int. J. Cancer 119, 2750–2759 (2006).
Pennacchietti, S. et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3, 347–361 (2003). This report shows that hypoxia controls MET expression in carcinoma and sarcoma cells, a finding with important consequences for therapy.
Scarpino, S. et al. Increased expression of Met protein is associated with up-regulation of hypoxia inducible factor-1 (HIF-1) in tumour cells in papillary carcinoma of the thyroid. J. Pathol. 202, 352–358 (2004).
Qian, F. et al. Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Res. 69, 8009–8016 (2009).
Nakagawa, T. et al. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 101, 210–215 (2010).
You, W. K. & McDonald, D. M. The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep. 41, 833–839 (2008).
Meiners, S., Brinkmann, V., Naundorf, H. & Birchmeier, W. Role of morphogenetic factors in metastasis of mammary carcinoma cells. Oncogene 16, 9–20 (1998).
Gallego, M. I., Bierie, B. & Hennighausen, L. Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways. Oncogene 22, 8498–8508 (2003).
Jeffers, M. et al. The mutationally activated Met receptor mediates motility and metastasis. Proc. Natl Acad. Sci. USA 95, 14417–14422 (1998).
Moshitch-Moshkovitz, S. et al. In vivo direct molecular imaging of early tumorigenesis and malignant progression induced by transgenic expression of GFP-Met. Neoplasia 8, 353–363 (2006).
Giordano, S. et al. A point mutation in the MET oncogene abrogates metastasis without affecting transformation. Proc. Natl Acad. Sci. USA 94, 13868–13872 (1997).
Muschel, R. J., Williams, J. E., Lowy, D. R. & Liotta, L. A. Harvey ras induction of metastatic potential depends upon oncogene activation and the type of recipient cell. Am. J. Pathol. 121, 1–8 (1985).
Webb, C. P. et al. Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis. Oncogene 17, 2019–2025 (1998).
Ridley, A. J., Comoglio, P. M. & Hall, A. Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. Mol. Cell. Biol. 15, 1110–1122 (1995).
Vermeulen, L. et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nature Cell Biol. 12, 468–476 (2010). A report describing stromal HGF/SF as a mesenchymal niche factor that cooperates with epithelial MET and WNT–β-catenin signalling in the maintenance of colon cancer stem cells.
Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730–737 (1997).
Kelly, P. N., Dakic, A., Adams, J. M., Nutt, S. L. & Strasser, A. Tumor growth need not be driven by rare cancer stem cells. Science 317, 337 (2007).
Malanchi, I. et al. Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling. Nature 452, 650–653 (2008).
Piccirillo, S. G. et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444, 761–765 (2006).
Wend, P., Holland, J. D., Ziebold, U. & Birchmeier, W. Wnt signaling in stem and cancer stem cells. Semin. Cell Dev. Biol. 21, 855–863 (2010).
Neuss, S., Becher, E., Woltje, M., Tietze, L. & Jahnen-Dechent, W. Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells 22, 405–414 (2004).
Son, B. R. et al. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 24, 1254–1264 (2006).
Tesio, M. et al. Enhanced c-Met activity promotes G.-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling. Blood 117, 419–428.
Urbanek, K. et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ. Res. 97, 663–673 (2005).
Tatsumi, R., Anderson, J. E., Nevoret, C. J., Halevy, O. & Allen, R. E. HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells. Dev. Biol. 194, 114–128 (1998).
Kamiya, A., Gonzalez, F. J. & Nakauchi, H. Identification and differentiation of hepatic stem cells during liver development. Front. Biosci. 11, 1302–1310 (2006).
Suzuki, A., Nakauchi, H. & Taniguchi, H. Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53, 2143–2152 (2004).
Barker, N. et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608–611 (2009).
Previdi, S. et al. Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and β-catenin/Wnt pathways. Eur. J. Cancer 46, 1679–1691 (2010).
Masuya, D. et al. The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients. Br. J. Cancer 90, 1555–1562 (2004).
Mahtouk, K., Tjin, E. P., Spaargaren, M. & Pals, S. T. The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas. Biochim. Biophys. Acta 1806, 208–219 (2010).
Sukhdeo, K. et al. Targeting the β-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc. Natl Acad. Sci. USA 104, 7516–7521 (2007).
Shia, S. et al. Conformational lability in serine protease active sites: structures of Hepatocyte Growth Factor Activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B. J. Mol. Biol. 346, 1335–1349 (2005).
Li, W. et al. Pegylated kunitz domain inhibitor suppresses hepsin-mediated invasive tumor growth and metastasis. Cancer Res. 69, 8395–8402 (2009).
Wu, Y. et al. Structural insight into distinct mechanisms of protease inhibition by antibodies. Proc. Natl Acad. Sci. USA 104, 19784–19789 (2007).
Ganesan, R. et al. Unraveling the allosteric mechanism of serine protease inhibition by an antibody. Structure 17, 1614–1624 (2009).
Farady, C. J., Sun, J., Darragh, M. R., Miller, S. M. & Craik, C. S. The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1). J. Mol. Biol. 369, 1041–1051 (2007).
Cao, B. et al. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc. Natl Acad. Sci. USA 98, 7443–7448 (2001).
Burgess, T. L. et al. Biochemical characterization of AMG 102: a neutralizing, fully human monoclonal antibody to human and nonhuman primate hepatocyte growth factor. Mol. Cancer Ther. 9, 400–409 (2010).
Jakubczak, J. L., LaRochelle, W. J. & Merlino, G. NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a partial agonist in vivo. Mol. Cell. Biol. 18, 1275–1283 (1998).
Tolbert, W. D. et al. A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist. Proc. Natl Acad. Sci. USA 104, 14592–14597 (2007).
Youles, M. et al. Engineering the NK1 fragment of hepatocyte growth factor/scatter factor as a MET receptor antagonist. J. Mol. Biol. 377, 616–622 (2008).
Otsuka, T. et al. Disassociation of met-mediated biological responses in vivo: the natural hepatocyte growth factor/scatter factor splice variant NK2 antagonizes growth but facilitates metastasis. Mol. Cell. Biol. 20, 2055–2065 (2000).
Date, K., Matsumoto, K., Shimura, H., Tanaka, M. & Nakamura, T. HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett. 420, 1–6 (1997).
Nakamura, T., Sakai, K. & Matsumoto, K. Anti-cancer approach with NK4: bivalent action and mechanisms. Anticancer Agents Med. Chem. 10, 36–46 (2010).
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).
Jin, H. et al. MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Res. 68, 4360–4368 (2008).
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).
Schelter, F. et al. A disintegrin and metalloproteinase-10 (ADAM-10) mediates DN30 antibody-induced shedding of the met surface receptor. J. Biol. Chem. 285, 26335–26340 (2010).
Pacchiana, G. et al. Monovalency unleashes the full therapeutic potential of the DN-30 anti-Met antibody. J. Biol. Chem. 285, 36149–36157 (2010).
Goetsch, L. Novel antibodies inhibitong c-met dimerization, and uses thereof (2007). http://ip.com/patapp/EP2188312A2.
Underiner, T. L., Herbertz, T. & Miknyoczki, S. J. Discovery of small molecule c-Met inhibitors: evolution and profiles of clinical candidates. Anticancer Agents Med. Chem. 10, 2188317–2188327 (2010).
Wang, W. et al. Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase. Proc. Natl Acad. Sci. USA 103, 3563–3568 (2006).
Rickert, K. W. et al. Structural basis for selective small-molecule kinase inhibition of activated c-Met. J. Biol. Chem. 286, 11218–11225 (2011).
Buchanan, S. G. et al. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol. Cancer Ther. 8, 3181–3190 (2009).
Timofeevski, S. L. et al. Enzymatic characterization of c-Met receptor tyrosine kinase oncogenic mutants and kinetic studies with aminopyridine and triazolopyrazine inhibitors. Biochemistry 48, 5339–5349 (2009).
Schroeder, G. M. et al. Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluor ophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J. Med. Chem. 52, 1251–1254 (2009).
D'Angelo, N. D. et al. Design, synthesis, and biological evaluation of potent c-Met inhibitors. J. Med. Chem. 51, 5766–5779 (2008).
Munshi, N. et al. ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity. Mol. Cancer Ther. 9, 1544–1553 (2010).
Eathiraj, S. et al. Discovery of a novel mode of protein kinase inhibition characterized by the mechanism of inhibition of human mesenchymal-epithelial transition factor (c-Met) protein autophosphorylation by ARQ 197. J. Biol. Chem. 286, 20666–20676 (2011).
Kwak, E. L. et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363, 1693–1703 (2010).
O'Brien, S. G. et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 348, 994–1004 (2003).
Knudsen, B. S. et al. A novel multipurpose monoclonal antibody for evaluating human c-Met expression in preclinical and clinical settings. Appl. Immunohistochem. Mol. Morphol. 17, 57–67 (2009).
Inoue, T. et al. Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue. Cancer Sci. 95, 803–808 (2004).
Mueller, K. L., Hunter, L. A., Ethier, S. P. & Boerner, J. L. Met and c-Src cooperate to compensate for loss of epidermal growth factor receptor kinase activity in breast cancer cells. Cancer Res. 68, 3314–3322 (2008).
Zhang, Y., Guessous, F., Kofman, A., Schiff, D. & Abounader, R. XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC. IDrugs 13, 112–121 (2010).
Cepero, V. et al. MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors. Cancer Res. 70, 7580–7590 (2010).
Corso, S. et al. Activation of HER family members in gastric carcinoma cells mediates resistance to MET inhibition. Mol. Cancer 9, 121 (2010).
Qi, J. et al. Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors. Cancer Res. 71, 1081–1091 (2011).
Spigel DR. et al. Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC. J. Clin. Oncol. Abstr. 29, 7505 (2011). References 166 and 167 are the first reports to demonstrate that combined treatment of subgroups of patients with NSCLC with EGFR and MET inhibitors increases progression-free survival and overall survival.
Iveson, T. et al. Safety and efficacy of epirubicin, cisplatin, and capecitabine (ECX) plus rilotumumab (R) as first-line treatment for unresectable locally advanced (LA) or metastatic (M) gastric or esophagogastric junction (EGJ) adenocarcinoma. Proc. Eur. Multidisc. Cancer Congr. Abstr. 6.504 (Stockholm, 2011).
Von Pawel J. et al. Final results from Arq 197–209: a global randomized placebo- controlled phase 2 clinical trial of erlotinib plus ARQ 197 versus erlotinib plus placebo in previously treated EGFR- inhibitor Naıve patients with advanced non-small cell lung cancer (NSCLC). J. Thoracic Oncol. Abstr. 5, 1 (2010).
Bagai, R., Fan, W. & Ma, P. C. ARQ-197, an oral small-molecule inhibitor of c-Met for the treatment of solid tumors. IDrugs 13, 404–414 (2010).
Gordon MS. et al. Activity of cabozantinib (XL184) in soft tissue and bone: results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors. J. Clin. Oncol. Abstr. 29, 3010 (2011).
Buckanovich RJ. et al. Activity of cabozantinib (XL184) in advanced ovarian cancer patients (pts): results from a phase II randomized discontinuation trial (RDT). J. Clin. Oncol. Abstr. 29, 5008 (2011).
Hussain M. et al. Cabozantinib (XL184) in metastatic castration-resistant prostate cancer (mCRPC): results from a phase II randomized discontinuation trial. J. Clin. Oncol. 29, 4516 (2011).
Kurzrock, R. et al. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J. Clin. Oncol. 29, 2660–2666 (2011).
Liu, L. et al. Synergistic effects of foretinib with HER-targeted agents in MET and HER1- or HER2-coactivated tumor cells. Mol. Cancer Ther. 10, 518–530 (2011).
Zhang, J. et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 463, 501–506 (2010).
Komada, M. et al. Proteolytic processing of the hepatocyte growth factor/scatter factor receptor by furin. FEBS Lett. 328, 25–29 (1993).
Gherardi, E. et al. Functional map and domain structure of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor. Proc. Natl Acad. Sci. USA 100, 12039–12044 (2003). This report defines the domain structure of extracellular MET through deletion mutagenesis and computational studies. The report establishes that MET contains a 7-balded β-propeller similar to the one present in the integrin α-chain.
Holmes, O. et al. Insights into the structure/function of hepatocyte growth factor/scatter factor from studies with individual domains. J. Mol. Biol. 367, 395–408 (2007).
DeLano, W. L. The PyMOL Molecular Graphics System. (DeLano Scientific, 2002).
Weidner, K. M., Behrens, J., Vandekerckhove, J. & Birchmeier, W. Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J. Cell Biol. 111, 2097–2108 (1990). This report demonstrates the first time that HGF/SF induces invasion of human carcinoma cells into three-dimensional matrices (that is, induces the invasive phenotype).
Rong, S. et al. Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. Mol. Cell. Biol. 12, 5152–5158 (1992).
Sakata, H. et al. Hepatocyte growth factor/scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers. Cell Growth Differ. 7, 1513–1523 (1996).
Itoh, M. et al. Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol. Cell. Biol. 20, 3695–3704 (2000).
Sachs, M. et al. Essential role of Gab1 for signaling by the c-Met receptor in vivo. J. Cell Biol. 150, 1375–1384 (2000).
Shen, Y., Naujokas, M., Park, M. & Ireton, K. InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase. Cell 103, 501–510 (2000).