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Gene Review

HGF  -  hepatocyte growth factor (hepapoietin A;...

Homo sapiens

Synonyms: DFNB39, F-TCF, HGFB, HPTA, Hepatocyte growth factor, ...
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Disease relevance of HGF


Psychiatry related information on HGF


High impact information on HGF

  • Here, we report the existence in the hepatocyte growth factor/scatter factor (HGF/SF) receptor of a multifunctional docking site made of the tandemly arranged degenerate sequence YVH/NV [8].
  • Inhibition of complex formation is sufficient to block HGF receptor internalization and to enhance HGF-induced signal transduction and biological responses [9].
  • Scatter factor is a fibroblast-derived modulator of epithelial cell mobility [10].
  • We identified a naturally occurring hepatocyte growth factor (HGF) variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule [11].
  • Here, we discuss the contribution of these and other signaling pathways and the role of HGF/SF and Met in the formation of epithelial cell tubules both in vitro in branching-morphogenesis assays and in vivo during organogenesis [12].

Chemical compound and disease context of HGF


Biological context of HGF

  • Hepatocyte growth factor (HGF) is a heterodimeric molecule composed of the alpha-chain containing the N-terminal hairpin domain, four kringle domains, and the serine protease-like beta-chain [17].
  • In contrast, transfection of the GabDeltaYXXP mutant abolished the elevation of Rap1.GTP by HGF [18].
  • Such apoptotic cell death was also induced by pretreatment of cells with a high concentration of HGF that downregulated endogenous p145(met) [19].
  • The ST8814 MPNST cell line also expresses all of these proteins, can convert pro-HGF to active HGF, and exhibits constitutive c-Met phosphorylation [4].
  • Exogenous HGF and KGF may be useful in corneal preservation and for regulating corneal wound healing [20].

Anatomical context of HGF


Associations of HGF with chemical compounds

  • The phosphorylated 145-kDa protein was identified as the beta-subunit of c-Met/hepatocyte growth factor (HGF) receptor, p145(met), in which tyrosine residues 1003, 1234, and 1235 were phosphorylated [19].
  • Nevertheless, Cu(2+) ions, competitive inhibitors for HGF-binding to p145(met), did not show any effect on cellular functions in serum-free conditions [19].
  • The effect of HGF on the growth of stromal cells alone or in combination with IL-6 or TNFalpha was examined in a bromodeoxyuridine (BrdU) incorporation study [22].
  • The invasion in the Matrigel assay stimulated by HGF was inhibited by protease inhibitors, aprotinin and FOY-305, as well as by anti-HGF antibody [23].
  • Immunohistochemical examination for the presence of PCNA and HGF, c-MET/HGF-receptor expression was performed on formalin-fixed samples from: a) sections of resected fragments of liver tissue remote from the tumor; b) tumor tissue; c) remnant liver, 30 min after hepatectomy; d) fine needle aspiration liver biopsy, 7 days after liver resection [24].
  • The NMR chemical shifts induced in NK1 (the truncated variant of HGF/SF comprised of the N-terminal and first Kringle domains) by titration with either heparin or DS oligosaccharides strongly indicate that both bind to essentially the same site [25].

Physical interactions of HGF

  • HGF/NK4 competitively inhibited the specific binding of HGF to the receptor [26].
  • Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor, which has been identified as the c-met protooncogene product [11].

Enzymatic interactions of HGF

  • Results obtained from in vitro experiments showed that urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) can cleave single-chain HGF [27].

Regulatory relationships of HGF


Other interactions of HGF

  • Human recombinant KGF and HGF/SF induced a concentration- and serum-dependent increase in rat alveolar type II cell DNA synthesis [32].
  • We conclude that Ras and Rac act downstream of the SF/HGF receptor p190Met to mediate cell spreading but that an additional signal is required to induce scattering [33].
  • Similarly, overexpression of dominant-negative forms of Cdk2 did not block SF/HGF-triggered cell cycle progression [34].
  • The amino acid sequence of HPTA/HGF recently became clear and revealed interesting structural homologies in a molecule that might become the largest known growth factor [35].
  • In this study, we investigated the effect of hepatocyte growth factor (HGF/SF) and epidermal growth factor (EGF) on adriamycin (ADR)-induced apoptosis [36].

Analytical, diagnostic and therapeutic context of HGF


  1. Rapid growth of invasive metastatic melanoma in carcinogen-treated hepatocyte growth factor/scatter factor-transgenic mice carrying an oncogenic CDK4 mutation. Tormo, D., Ferrer, A., Gaffal, E., Wenzel, J., Basner-Tschakarjan, E., Steitz, J., Heukamp, L.C., Gütgemann, I., Buettner, R., Malumbres, M., Barbacid, M., Merlino, G., Tüting, T. Am. J. Pathol. (2006) [Pubmed]
  2. The hepatocyte growth factor regulatory factors in human breast cancer. Parr, C., Watkins, G., Mansel, R.E., Jiang, W.G. Clin. Cancer Res. (2004) [Pubmed]
  3. Hepatocyte growth factor activation inhibitors (HAI-1 and HAI-2) regulate HGF-induced invasion of human breast cancer cells. Parr, C., Jiang, W.G. Int. J. Cancer (2006) [Pubmed]
  4. CD44-independent hepatocyte growth factor/c-Met autocrine loop promotes malignant peripheral nerve sheath tumor cell invasion in vitro. Su, W., Gutmann, D.H., Perry, A., Abounader, R., Laterra, J., Sherman, L.S. Glia (2004) [Pubmed]
  5. Predictive value of plasma hepatocyte growth factor/scatter factor levels in patients with clinically localized prostate cancer. Gupta, A., Karakiewicz, P.I., Roehrborn, C.G., Lotan, Y., Zlotta, A.R., Shariat, S.F. Clin. Cancer Res. (2008) [Pubmed]
  6. Hepatocyte growth factor (HGF/SF) in Alzheimer's disease. Fenton, H., Finch, P.W., Rubin, J.S., Rosenberg, J.M., Taylor, W.G., Kuo-Leblanc, V., Rodriguez-Wolf, M., Baird, A., Schipper, H.M., Stopa, E.G. Brain Res. (1998) [Pubmed]
  7. Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma. Tolnay, E., Kuhnen, C., Wiethege, T., König, J.E., Voss, B., Müller, K.M. J. Cancer Res. Clin. Oncol. (1998) [Pubmed]
  8. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Ponzetto, C., Bardelli, A., Zhen, Z., Maina, F., dalla Zonca, P., Giordano, S., Graziani, A., Panayotou, G., Comoglio, P.M. Cell (1994) [Pubmed]
  9. The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Petrelli, A., Gilestro, G.F., Lanzardo, S., Comoglio, P.M., Migone, N., Giordano, S. Nature (2002) [Pubmed]
  10. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Stoker, M., Gherardi, E., Perryman, M., Gray, J. Nature (1987) [Pubmed]
  11. Identification of a competitive HGF antagonist encoded by an alternative transcript. Chan, A.M., Rubin, J.S., Bottaro, D.P., Hirschfield, D.W., Chedid, M., Aaronson, S.A. Science (1991) [Pubmed]
  12. How to make tubes: signaling by the Met receptor tyrosine kinase. Rosário, M., Birchmeier, W. Trends Cell Biol. (2003) [Pubmed]
  13. Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast cancer cells: implications for tumour-stroma interactions. Hiscox, S., Jordan, N.J., Jiang, W., Harper, M., McClelland, R., Smith, C., Nicholson, R.I. Endocr. Relat. Cancer (2006) [Pubmed]
  14. Immunohistochemical expression of hepatocyte growth factor and c-Met/HGF receptor in benign and malignant human prostate tissue. Nakashiro, K., Hayashi, Y., Oyasu, R. Oncol. Rep. (2003) [Pubmed]
  15. Altered gene expression pattern in cultured human breast cancer cells treated with hepatocyte growth factor/scatter factor in the setting of DNA damage. Yuan, R., Fan, S., Achary, M., Stewart, D.M., Goldberg, I.D., Rosen, E.M. Cancer Res. (2001) [Pubmed]
  16. Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents. Fan, S., Wang, J.A., Yuan, R.Q., Rockwell, S., Andres, J., Zlatapolskiy, A., Goldberg, I.D., Rosen, E.M. Oncogene (1998) [Pubmed]
  17. Cooperative interaction between alpha- and beta-chains of hepatocyte growth factor on c-Met receptor confers ligand-induced receptor tyrosine phosphorylation and multiple biological responses. Matsumoto, K., Kataoka, H., Date, K., Nakamura, T. J. Biol. Chem. (1998) [Pubmed]
  18. Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL. Sakkab, D., Lewitzky, M., Posern, G., Schaeper, U., Sachs, M., Birchmeier, W., Feller, S.M. J. Biol. Chem. (2000) [Pubmed]
  19. Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells. Yamamoto, N., Mammadova, G., Song, R.X., Fukami, Y., Sato, K. J. Cell. Sci. (2006) [Pubmed]
  20. Hepatocyte growth factor, keratinocyte growth factor, their receptors, fibroblast growth factor receptor-2, and the cells of the cornea. Wilson, S.E., Walker, J.W., Chwang, E.L., He, Y.G. Invest. Ophthalmol. Vis. Sci. (1993) [Pubmed]
  21. NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells. Maehara, N., Matsumoto, K., Kuba, K., Mizumoto, K., Tanaka, M., Nakamura, T. Br. J. Cancer (2001) [Pubmed]
  22. Interleukin-6- and tumour necrosis factor alpha-mediated expression of hepatocyte growth factor by stromal cells and its involvement in the growth of endometriosis. Khan, K.N., Masuzaki, H., Fujishita, A., Kitajima, M., Hiraki, K., Sekine, I., Matsuyama, T., Ishimaru, T. Hum. Reprod. (2005) [Pubmed]
  23. Hepatocyte growth factor stimulates the invasion of gallbladder carcinoma cell lines in vitro. Li, H., Shimura, H., Aoki, Y., Date, K., Matsumoto, K., Nakamura, T., Tanaka, M. Clin. Exp. Metastasis (1998) [Pubmed]
  24. Hepatocyte growth factor levels in liver and blood, and post-operative liver cell proliferation in patients with benign and malignant liver tumors after partial hepatectomy. Dłuzniewska, J., Zolich, D., Polański, J., Zajac, L., Sitkiewicz, D., Łukomska, B. Med. Sci. Monit. (2002) [Pubmed]
  25. The binding properties of minimal oligosaccharides reveal a common heparan sulfate/dermatan sulfate-binding site in hepatocyte growth factor/scatter factor that can accommodate a wide variety of sulfation patterns. Deakin, J.A., Blaum, B.S., Gallagher, J.T., Uhrín, D., Lyon, M. J. Biol. Chem. (2009) [Pubmed]
  26. HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. Date, K., Matsumoto, K., Shimura, H., Tanaka, M., Nakamura, T. FEBS Lett. (1997) [Pubmed]
  27. Hepatocyte growth factor plasma levels after myocardial infarction are not affected by recombinant tissue-type plasminogen-activator therapy. Molnar, C., Buratti, T., Wiedermann, C.J., Tilg, H. Eur. Cytokine Netw. (2000) [Pubmed]
  28. Scatter factor binds to thrombospondin and other extracellular matrix components. Lamszus, K., Joseph, A., Jin, L., Yao, Y., Chowdhury, S., Fuchs, A., Polverini, P.J., Goldberg, I.D., Rosen, E.M. Am. J. Pathol. (1996) [Pubmed]
  29. Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP. Hamasuna, R., Kataoka, H., Moriyama, T., Itoh, H., Seiki, M., Koono, M. Int. J. Cancer (1999) [Pubmed]
  30. Expression of hepatocyte growth factor/scatter factor and c-Met in human dental papilla and fibroblasts from dental papilla. Kajihara, T., Ohnishi, T., Arakaki, N., Semba, I., Daikuhara, Y. Arch. Oral Biol. (1999) [Pubmed]
  31. Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review). Moriyama, T., Kataoka, H., Koono, M., Wakisaka, S. Int. J. Mol. Med. (1999) [Pubmed]
  32. Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium. Panos, R.J., Rubin, J.S., Csaky, K.G., Aaronson, S.A., Mason, R.J. J. Clin. Invest. (1993) [Pubmed]
  33. Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. Ridley, A.J., Comoglio, P.M., Hall, A. Mol. Cell. Biol. (1995) [Pubmed]
  34. Scatter factor/hepatocyte growth factor stimulation of glioblastoma cell cycle progression through G(1) is c-Myc dependent and independent of p27 suppression, Cdk2 activation, or E2F1-dependent transcription. Walter, K.A., Hossain, M.A., Luddy, C., Goel, N., Reznik, T.E., Laterra, J. Mol. Cell. Biol. (2002) [Pubmed]
  35. Liver regeneration: molecular mechanisms of growth control. Michalopoulos, G.K. FASEB J. (1990) [Pubmed]
  36. Suppression of adriamycin-induced apoptosis by sustained activation of the phosphatidylinositol-3'-OH kinase-Akt pathway. Takeuchi, K., Ito, F. J. Biol. Chem. (2004) [Pubmed]
  37. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Wang, M., Crisostomo, P.R., Herring, C., Meldrum, K.K., Meldrum, D.R. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  38. 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. Neuss, S., Becher, E., Wöltje, M., Tietze, L., Jahnen-Dechent, W. Stem Cells (2004) [Pubmed]
  39. Transfection of human hepatocyte growth factor gene ameliorates secondary lymphedema via promotion of lymphangiogenesis. Saito, Y., Nakagami, H., Morishita, R., Takami, Y., Kikuchi, Y., Hayashi, H., Nishikawa, T., Tamai, K., Azuma, N., Sasajima, T., Kaneda, Y. Circulation (2006) [Pubmed]
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