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HGF/c-MET Signaling in Advanced Cancers

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Cancer Genome and Tumor Microenvironment

Part of the book series: Cancer Genetics ((CANGENETICS))

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Abstract

Papillary renal carcinoma (RCCP) is histologically and genetically distinct from other forms of inherited renal carcinoma (e.g., von Hippel–Lindau disease, which is caused by inactivation of the VHL gene –( see Chapter 6). RCCP genes map to several loci; one of each on 7q31.1-q34 encodes the c-Met oncoprotein (Schmidt et al. 1997). In the original publication, missense mutations in the tyrosine kinase domain of the MET gene were found both in the germlines of affected patients and in a subset of sporadic papillary renal carcinomas. Additionally, tumors from RCCP patients commonly show trisomy of chromosome 7 harboring non-random duplication of the mutant MET allele (Zhuang et al. 1998).

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References

  • Adebonojo SA, Bowser AN, Moritz DM, Corcoran PC (1999) Impact of revised stage classification of lung cancer on survival: a military experience. Chest 115:1507–1513.

    Article  PubMed  CAS  Google Scholar 

  • Aebersold DM, Kollar A, Beer KT, Laissue J, Greiner RH, Djonov V (2001) Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation. Int J Cancer 96:41–54.

    Article  PubMed  CAS  Google Scholar 

  • Aebersold DM, Landt O, Berthou S, Gruber G, Beer KT, Greiner RH, Zimmer Y (2003) Prevalence and clinical impact of Met Y1253D-activating point mutation in radiotherapy-treated squamous cell cancer of the oropharynx. Oncogene 22:8519–8523.

    Article  PubMed  CAS  Google Scholar 

  • Atabey N, Gao Y, Yao ZJ, Breckenridge D, Soon L, Soriano JV, Burke TR Jr, Bottaro DP (2001) 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.

    PubMed  CAS  Google Scholar 

  • Bardelli A, Longati P, Williams TA, Benvenuti S, Comoglio PM (1999) A peptide representing the carboxyl-terminal tail of the met receptor inhibits kinase activity and invasive growth. J Biol Chem 274:29274–29281.

    Article  PubMed  CAS  Google Scholar 

  • Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A 104:20932–20937.

    Article  PubMed  CAS  Google Scholar 

  • Bergot E, Richard N, Zalcman G (2007) [Mechanisms of action of targeted therapies ... and mechanisms of resistance]. Rev Mal Respir 24:6S180–187.

    PubMed  CAS  Google Scholar 

  • Beviglia L, Matsumoto K, Lin CS, Ziober BL, Kramer RH (1997) Expression of the c-Met/HGF receptor in human breast carcinoma: correlation with tumor progression. Int J Cancer 74:301–309.

    Article  PubMed  CAS  Google Scholar 

  • Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251:802–804.

    Article  PubMed  CAS  Google Scholar 

  • Bowers DC, Fan S, Walter KA, Abounader R, Williams JA, Rosen EM, Laterra J (2000) Scatter factor/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways. Cancer Res 60:4277–4283.

    PubMed  CAS  Google Scholar 

  • Cantrell DA (2001) Phosphoinositide 3-kinase signalling pathways. J Cell Sci 114:1439–1445

    PubMed  CAS  Google Scholar 

  • Cattley RC and Radinsky RR (2004) Cancer therapeutics: understanding the mechanism of action. Toxicol Pathol 32 Suppl 1:116–121.

    Google Scholar 

  • Christensen JG, Schreck R, Burrows J, Kuruganti P, Chan E, Le P, Chen J, Wang X, Ruslim L, Blake R, Lipson KE, Ramphal J, Do S, Cui JJ, Cherrington JM, Mendel DB (2003) 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.

    PubMed  CAS  Google Scholar 

  • Christensen JG, Burrows J, Salgia R (2005) c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett 225:1–26.

    Article  PubMed  CAS  Google Scholar 

  • Chute JP, Chen T, Feigal E, Simon R, Johnson BE (1999) Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol 17:1794–1801.

    PubMed  CAS  Google Scholar 

  • Comoglio PM (1993) Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells. Exs 65:131–165.

    PubMed  CAS  Google Scholar 

  • Cooper CS, Park M, Blair DG, Tainsky MA, Huebner K, Croce CM, Vande Woude GF (1984) Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311:29–33.

    Article  PubMed  CAS  Google Scholar 

  • Davies G, Jiang WG, Mason MD (2001) HGF/SF modifies the interaction between its receptor c-Met, and the E-cadherin/catenin complex in prostate cancer cells. Int J Mol Med 7:385–388.

    PubMed  CAS  Google Scholar 

  • Derman MP, Cunha MJ, Barros EJ, Nigam SK, Cantley LG (1995) HGF-mediated chemotaxis and tubulogenesis require activation of the phosphatidylinositol 3-kinase. Am J Physiol 268:F1211–1217.

    PubMed  CAS  Google Scholar 

  • Di Renzo MF, Olivero M, Martone T, Maffe A, Maggiora P, Stefani AD, Valente G, Giordano S, Cortesina G, Comoglio PM (2000) Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 19:1547–1555.

    Article  PubMed  CAS  Google Scholar 

  • Eliceiri BP, Klemke R, Stromblad S, Cheresh DA (1998) Integrin alphavbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis. J Cell Biol 140:1255–1263.

    Article  PubMed  CAS  Google Scholar 

  • Ellison DH and Berl T (2007) Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med 356:2064–2072.

    Article  PubMed  CAS  Google Scholar 

  • Fidler IJ, Yano S, Zhang RD, Fujimaki T, Bucana CD (2002) The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol 3:53–57.

    Article  PubMed  CAS  Google Scholar 

  • Furge KA, Zhang YW, Vande Woude GF (2000) Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 19:5582–5589.

    Article  PubMed  CAS  Google Scholar 

  • Furge KA, Kiewlich D, Le P, Vo MN, Faure M, Howlett AR, Lipson KE, Woude GF, Webb CP (2001) Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of the Met receptor tyrosine kinase. Proc Natl Acad Sci U S A 98:10722–10727.

    Article  PubMed  CAS  Google Scholar 

  • Gherardi E, Sandin S, Petoukhov MV, Finch J, Youles ME, Ofverstedt LG, Miguel RN, Blundell TL, Vande Woude GF, Skoglund U, Svergun DI (2006) Structural basis of hepatocyte growth factor/scatter factor and MET signalling. Proc Natl Acad Sci U S A 103:4046–4051.

    Article  PubMed  CAS  Google Scholar 

  • Gohda E, Matsunaga T, Kataoka H, Takebe T, Yamamoto I (1994) Induction of hepatocyte growth factor in human skin fibroblasts by epidermal growth factor, platelet-derived growth factor and fibroblast growth factor. Cytokine 6:633–640.

    Article  PubMed  CAS  Google Scholar 

  • Graziani A, Gramaglia D, dalla Zonca P, Comoglio PM (1993) Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger. J Biol Chem 268:9165–9168.

    PubMed  CAS  Google Scholar 

  • Griffioen AW and Molema G (2000) Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev 52:237–268.

    PubMed  CAS  Google Scholar 

  • Gu H and Neel BG (2003) The “Gab” in signal transduction. Trends Cell Biol 13:122–130.

    Article  PubMed  CAS  Google Scholar 

  • Gual P, Giordano S, Williams TA, Rocchi S, Van Obberghen E, Comoglio PM (2000) Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis. Oncogene 19:1509–1518.

    Article  PubMed  CAS  Google Scholar 

  • Gual P, Giordano S, Anguissola S, Parker PJ, Comoglio PM (2001) Gab1 phosphorylation: a novel mechanism for negative regulation of HGF receptor signaling. Oncogene 20:156–166.

    Article  PubMed  CAS  Google Scholar 

  • Hagel M, George EL, Kim A, Tamimi R, Opitz SL, Turner CE, Imamoto A, Thomas SM (2002) The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. Mol Cell Biol 22:901–915.

    Article  PubMed  CAS  Google Scholar 

  • Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25.

    Article  PubMed  CAS  Google Scholar 

  • Ichimura E, Maeshima A, Nakajima T, Nakamura T (1996) Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res 87:1063–1069.

    PubMed  CAS  Google Scholar 

  • Jafri NF, Ma PC, Maulik G, Salgia R (2003) Mechanisms of metastasis as related to receptor tyrosine kinases in small-cell lung cancer. J Environ Pathol Toxicol Oncol 22:147–165.

    Article  PubMed  CAS  Google Scholar 

  • Jagadeeswaran R, Surawska H, Krishnaswamy S, Janamanchi V, Mackinnon AC, Seiwert TY, Loganathan S, Kanteti R, Reichman T, Nallasura V, Schwartz S, Faoro L, Wang YC, Girard L, Tretiakova MS, Ahmed S, Zumba O, Soulii L, Bindokas VP, Szeto LL, Gordon GJ, Bueno R, Sugarbaker D, Lingen MW, Sattler M, Krausz T, Vigneswaran W, Natarajan V, Minna J, Vokes EE, Ferguson MK, Husain AN, Salgia R (2008) Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion. Cancer Res 68:132–142.

    Article  PubMed  CAS  Google Scholar 

  • Jeffers M, Rong S, Vande Woude GF (1996) Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factor-met signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol Cell Biol 16:1115–1125.

    PubMed  CAS  Google Scholar 

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66.

    Article  PubMed  Google Scholar 

  • Jiang WG, Hiscox SE, Parr C, Martin TA, Matsumoto K, Nakamura T, Mansel RE (1999) Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Clin Cancer Res 5:3695–3703.

    PubMed  CAS  Google Scholar 

  • Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, Silberman S, Capdeville R, Dimitrijevic S, Druker B, Demetri GD (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056.

    Article  PubMed  CAS  Google Scholar 

  • Jun HT, Sun J, Rex K, Radinsky R, Kendall R, Coxon A, Burgess TL (2007) 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.

    Article  PubMed  CAS  Google Scholar 

  • Kaji M, Yonemura Y, Harada S, Liu X, Terada I, Yamamoto H (1996) Participation of c-met in the progression of human gastric cancers: anti-c-met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells. Cancer Gene Ther 3:393–404.

    PubMed  CAS  Google Scholar 

  • Koochekpour S, Jeffers M, Wang PH, Gong C, Taylor GA, Roessler LM, Stearman R, Vasselli JR, Stetler-Stevenson WG, Kaelin WG Jr, Linehan WM, Klausner RD, Gnarra JR, Vande Woude GF (1999) The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells. Mol Cell Biol 19:5902–5912.

    PubMed  CAS  Google Scholar 

  • Kuniyasu H, Yasui W, Kitadai Y, Yokozaki H, Ito H, Tahara E (1992) Frequent amplification of the c-met gene in scirrhous type stomach cancer. Biochem Biophys Res Commun 189:227–232.

    Article  PubMed  CAS  Google Scholar 

  • Kuniyasu H, Yasui W, Yokozaki H, Kitadai Y, Tahara E (1993) Aberrant expression of c-met mRNA in human gastric carcinomas. Int J Cancer 55:72–75.

    Article  PubMed  CAS  Google Scholar 

  • Kurayoshi M, Oue N, Yamamoto H, Kishida M, Inoue A, Asahara T, Yasui W, Kikuchi A (2006) Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res 66:10439–10448.

    Article  PubMed  CAS  Google Scholar 

  • Lai JF, Kao SC, Jiang ST, Tang MJ, Chan PC, Chen HC (2000) Involvement of focal adhesion kinase in hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells. J Biol Chem 275:7474–7480.

    Article  PubMed  CAS  Google Scholar 

  • Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, Schmidt L, Zbar B, Vande Woude GF (2000) A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19:4947–4953.

    Article  PubMed  CAS  Google Scholar 

  • Legros L, Bourcier C, Jacquel A, Mahon FX, Cassuto JP, Auberger P, Pagès G (2004) Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia. Blood 104:495–501.

    Article  PubMed  CAS  Google Scholar 

  • Liu Y (1998) The human hepatocyte growth factor receptor gene: complete structural organization and promoter characterization. Gene 215:159–169.

    Article  PubMed  CAS  Google Scholar 

  • Liu C and Tsao MS (1993) In vitro and in vivo expressions of transforming growth factor-alpha and tyrosine kinase receptors in human non-small-cell lung carcinomas. Am J Pathol 142:1155–1162.

    PubMed  CAS  Google Scholar 

  • Liu Z, Greco AJ, Hellman NE, Spector J, Robinson J, Tang OT, Lipschutz JH (2007) Intracellular signaling via ERK/MAPK completes the pathway for tubulogenic fibronectin in MDCK cells. Biochem Biophys Res Commun 353:793–798.

    Article  PubMed  CAS  Google Scholar 

  • Lorenzato A, Olivero M, Patanè S, Rosso E, Oliaro A, Comoglio PM, Di Renzo MF (2002) Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion. Cancer Res 62:7025–7030.

    PubMed  CAS  Google Scholar 

  • Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4:257–262.

    Article  PubMed  CAS  Google Scholar 

  • Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, Johnson BE, Salgia R (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63:6272–6281.

    PubMed  CAS  Google Scholar 

  • Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, Fox EA, Hansen M, Schaefer E, Naoki K, Lader A, Richards W, Sugarbaker D, Husain AN, Christensen JG, Salgia R (2005a) Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 65:1479–1488.

    Article  PubMed  CAS  Google Scholar 

  • Ma PC, Schaefer E, Christensen JG, Salgia R (2005b) A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin. Clin Cancer Res 11:2312–2319.

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto K, Matsumoto K, Nakamura T, Kramer RH (1994) Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells. J Biol Chem 269:31807–31813.

    PubMed  CAS  Google Scholar 

  • Matsumoto K, Ziober BL, Yao CC, Kramer RH (1995) Growth factor regulation of integrin-mediated cell motility. Cancer Metastasis Rev 14:205–217.

    Article  PubMed  CAS  Google Scholar 

  • Maulik G, Kijima T, Ma PC, Ghosh SK, Lin J, Shapiro GI, Schaefer E, Tibaldi E, Johnson BE, Salgia R (2002a) Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res 8:620–627.

    PubMed  CAS  Google Scholar 

  • Maulik G, Shrikhande A, Kijima T, Ma PC, Morrison PT, Salgia R (2002b) Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev 13:41–59.

    Article  PubMed  CAS  Google Scholar 

  • McAuliffe JC, Lazar AJ, Yang D, Steinert DM, Qiao W, Thall PF, Raymond AK, Benjamin RS, Trent JC (2007) Association of intratumoral vascular endothelial growth factor expression and clinical outcome for patients with gastrointestinal stromal tumors treated with imatinib mesylate. Clin Cancer Res 13:6727–6734.

    Article  PubMed  CAS  Google Scholar 

  • Michieli P, Basilico C, Pennacchietti S, Maffè A, Tamagnone L, Giordano S, Bardelli A, Comoglio PM (1999) Mutant Met-mediated transformation is ligand-dependent and can be inhibited by HGF antagonists. Oncogene 18:5221–5231.

    Article  PubMed  CAS  Google Scholar 

  • Murray N, Salgia R, Fossella FV (2004) Targeted molecules in small cell lung cancer. Semin Oncol 31:106–111.

    Article  PubMed  CAS  Google Scholar 

  • Nabeshima K, Shimao Y, Inoue T, Itoh H, Kataoka H, Koono M (1998) Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells. Int J Cancer 78:750–759.

    Article  PubMed  CAS  Google Scholar 

  • Neckers L, Schulte TW, Mimnaugh E (1999) Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs 17:361–373.

    Article  PubMed  CAS  Google Scholar 

  • Nobes CD and Hall A (1999) Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol 144:1235–1244.

    Article  PubMed  CAS  Google Scholar 

  • O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994–1004.

    Article  PubMed  Google Scholar 

  • Olivero M, Rizzo M, Madeddu R, Casadio C, Pennacchietti S, Nicotra MR, Prat M, Maggi G, Arena N, Natali PG, Comoglio PM, Di Renzo MF (1996) Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br J Cancer 74:1862–1868.

    Article  PubMed  CAS  Google Scholar 

  • Otsuka T, Jakubczak J, Vieira W, Bottaro DP, Breckenridge D, Larochelle WJ, Merlino G (2000) 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.

    Article  PubMed  CAS  Google Scholar 

  • Park WS, Oh RR, Kim YS, Park JY, Shin MS, Lee HK, Lee SH, Yoo NJ, Lee JY (2000) Absence of mutations in the kinase domain of the Met gene and frequent expression of Met and HGF/SF protein in primary gastric carcinomas. Apmis 108:195–200.

    Article  PubMed  CAS  Google Scholar 

  • Parr C, Hiscox S, Nakamura T, Matsumoto K, Jiang WG (2000) Nk4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the motility and invasion of colon cancer cells. Int J Cancer 85:563–570.

    Article  PubMed  CAS  Google Scholar 

  • Parr C, Davies G, Nakamura T, Matsumoto K, Mason MD, Jiang WG (2001) The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant. Biochem Biophys Res Commun 285:1330–1337.

    Article  PubMed  CAS  Google Scholar 

  • Puri N, Khramtsov A, Ahmed S, Nallasura V, Hetzel JT, Jagadeeswaran R, Karczmar G, Salgia R (2007) A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res 67:3529–3534.

    Article  PubMed  CAS  Google Scholar 

  • Rahimi N, Hung W, Tremblay E, Saulnier R, Elliott B (1998) c-Src kinase activity is required for hepatocyte growth factor-induced motility and anchorage-independent growth of mammary carcinoma cells. J Biol Chem 273:33714–33721.

    Article  PubMed  CAS  Google Scholar 

  • Rosen EM, Meromsky L, Setter E, Vinter DW, Goldberg ID (1990) Purified scatter factor stimulates epithelial and vascular endothelial cell migration. Proc Soc Exp Biol Med 195:34–43.

    PubMed  CAS  Google Scholar 

  • Rosen EM, Lamszus K, Laterra J, Polverini PJ, Rubin JS, Goldberg ID (1997) HGF/SF in angiogenesis. Ciba Found Symp 212:215–226; discussion 227–219.

    PubMed  CAS  Google Scholar 

  • Sachs M, Brohmann H, Zechner D, Müller T, Hülsken J, Walther I, Schaeper U, Birchmeier C, Birchmeier W (2000) Essential role of Gab1 for signaling by the c-Met receptor in vivo. J Cell Biol 150:1375–1384.

    Article  PubMed  CAS  Google Scholar 

  • Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (2000) Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. J Biol Chem 275:10772–10778.

    Article  PubMed  CAS  Google Scholar 

  • Salgia R, Li JL, Ewaniuk DS, Wang YB, Sattler M, Chen WC, Richards W, Pisick E, Shapiro GI, Rollins BJ, Chen LB, Griffin JD, Sugarbaker DJ (1999) Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility. Oncogene 18:67–77.

    Article  PubMed  CAS  Google Scholar 

  • Salgia RS, S. Hong, D.S. Ng, C.S. Frye, J. Janisch, L. Ratain, M.J. Kurzrock, R (2008) A phase I study of XL184, a RET, VEGFR2, and MET kinase inhibitor, in patients (pts) with advanced malignancies, including pts with medullary thyroid cancer (MTC). J Clin Oncol 26:2008 (May 20 suppl; abstr 3522).

    Google Scholar 

  • Sattler M and Salgia R (2007) c-Met and hepatocyte growth factor: potential as novel targets in cancer therapy. Curr Oncol Rep 9:102–108.

    Article  PubMed  CAS  Google Scholar 

  • Sattler M, Pride YB, Ma P, Gramlich JL, Chu SC, Quinnan LA, Shirazian S, Liang C, Podar K, Christensen JG, Salgia R (2003) A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer Res 63: 5462–5469.

    PubMed  CAS  Google Scholar 

  • Schaller MD and Sasaki T (1997) Differential signaling by the focal adhesion kinase and cell adhesion kinase beta. J Biol Chem 272:25319–25325.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT, Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC, Geil L, Orcutt ML, Stackhouse T, Lipan J, Slife L, Brauch H, Decker J, Niehans G, Hughson MD, Moch H, Storkel S, Lerman MI, Linehan WM, Zbar B (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16:68–73.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt L, Junker K, Weirich G, Glenn G, Choyke P, Lubensky I, Zhuang Z, Jeffers M, Vande Woude G, Neumann H, Walther M, Linehan WM, Zbar B (1998) Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Res 58:1719–1722.

    PubMed  CAS  Google Scholar 

  • Seki T, Hagiya M, Shimonishi M, Nakamura T, Shimizu S (1991) Organization of the human hepatocyte growth factor-encoding gene. Gene 102:213–219.

    Article  PubMed  CAS  Google Scholar 

  • Sengupta S, Gherardi E, Sellers LA, Wood JM, Sasisekharan R, Fan TP (2003) Hepatocyte growth factor/scatter factor can induce angiogenesis independently of vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 23:69–75.

    Article  PubMed  CAS  Google Scholar 

  • Siddiqui SS, Loganathan S, Krishnaswamy S, Faoro L, Jagadeeswaran R, Salgia R (2008) C. elegans as a model organism for in vivo screening in cancer: effects of human c-Met in lung cancer affect C. elegans vulva phenotypes. Cancer Biol Ther 7.

    Google Scholar 

  • Siegfried JM, Weissfeld LA, Singh-Kaw P, Weyant RJ, Testa JR, Landreneau RJ (1997) Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. Cancer Res 57:433–439.

    PubMed  CAS  Google Scholar 

  • Siegfried JM, Weissfeld LA, Luketich JD, Weyant RJ, Gubish CT, Landreneau RJ (1998) The clinical significance of hepatocyte growth factor for non-small cell lung cancer. Ann Thorac Surg 66:1915–1918.

    Article  PubMed  CAS  Google Scholar 

  • Sugimura H, Nichols FC, Yang P, Allen MS, Cassivi SD, Deschamps C, Williams BA, Pairolero PC (2007) Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Ann Thorac Surg 83:409–417; discussion 417–408.

    Article  PubMed  Google Scholar 

  • Takaishi K, Sasaki T, Kato M, Yamochi W, Kuroda S, Nakamura T, Takeichi M, Takai Y (1994) Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF-induced cell motility. Oncogene 9:273–279.

    PubMed  CAS  Google Scholar 

  • Takanami I, Tanana F, Hashizume T, Kikuchi K, Yamamoto Y, Yamamoto T, Kodaira S (1996) Hepatocyte growth factor and c-Met/hepatocyte growth factor receptor in pulmonary adenocarcinomas: an evaluation of their expression as prognostic markers. Oncology 53:392–397.

    Article  PubMed  CAS  Google Scholar 

  • Tamagnone L and Comoglio PM (2000) Signalling by semaphorin receptors: cell guidance and beyond. Trends Cell Biol 10:377–383.

    Article  PubMed  CAS  Google Scholar 

  • Tokunou M, Niki T, Eguchi K, Iba S, Tsuda H, Yamada T, Matsuno Y, Kondo H, Saitoh Y, Imamura H, Hirohashi S (2001) c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma. Am J Pathol 158:1451–1463.

    Article  PubMed  CAS  Google Scholar 

  • Trusolino L, Serini G, Cecchini G, Besati C, Ambesi-Impiombato FS, Marchisio PC, De Filippi R (1998) Growth factor-dependent activation of alphavbeta3 integrin in normal epithelial cells: implications for tumor invasion. J Cell Biol 142:1145–1156.

    Article  PubMed  CAS  Google Scholar 

  • Uemura N, Salgia R, Li JL, Pisick E, Sattler M, Griffin JD (1997) The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins. Leukemia 11:376–385.

    Article  PubMed  CAS  Google Scholar 

  • Van Belle E, Witzenbichler B, Chen D, Silver M, Chang L, Schwall R, Isner JM (1998) Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: the case for paracrine amplification of angiogenesis. Circulation 97:381–390.

    PubMed  Google Scholar 

  • Webb CP, Hose CD, Koochekpour S, Jeffers M, Oskarsson M, Sausville E, Monks A, Vande Woude GF (2000) The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network. Cancer Res 60:342–349.

    PubMed  CAS  Google Scholar 

  • Wojta J, Kaun C, Breuss JM, Koshelnick Y, Beckmann R, Hattey E, Mildner M, Weninger W, Nakamura T, Tschachler E, Binder BR (1999) Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Lab Invest 79:427–438.

    PubMed  CAS  Google Scholar 

  • Xiao GH, Jeffers M, Bellacosa A, Mitsuuchi Y, Vande Woude GF, Testa JR (2001) Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A 98:247–252.

    Article  PubMed  CAS  Google Scholar 

  • Zeng ZJ, Yang LY, Ding X, Wang W (2004) Expressions of cysteine-rich61, connective tissue growth factor and Nov genes in hepatocellular carcinoma and their clinical significance. World J Gastroenterol 10:3414–3418.

    PubMed  CAS  Google Scholar 

  • Zhang YW, Su Y, Volpert OV, Vande Woude GF (2003) Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc Natl Acad Sci U S A 100:12718–12723.

    Article  PubMed  CAS  Google Scholar 

  • Zhuang Z, Park WS, Pack S, Schmidt L, Vortmeyer AO, Pak E, Pham T, Weil RJ, Candidus S, Lubensky IA, Linehan WM, Zbar B, Weirich G (1998) Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas. Nat Genet 20:66–69.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of Chicago, Chicago, IL, USA

    Mandira Ray & J G Garcia

  2. Department of Medicine, University of Chicago, 5841 South Maryland Ave, Chicago, IL, USA

    Ravi Salgia

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  1. Mandira Ray
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  2. J G Garcia
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  3. Ravi Salgia
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Correspondence to Ravi Salgia .

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  1. Children's Hospital of Philadelphia, Civic Center Blvd. 3615, Philadelphia, 19104, U.S.A.

    Andrei Thomas-Tikhonenko

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Ray, M., Garcia, J.G., Salgia, R. (2010). HGF/c-MET Signaling in Advanced Cancers. In: Thomas-Tikhonenko, A. (eds) Cancer Genome and Tumor Microenvironment. Cancer Genetics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0711-0_12

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