Skip to main content
SpringerLink
Log in

Pericellular Activation of Peptide Growth Factors by Serine Proteases

  • Chapter
  • First Online:
Regulation of Signal Transduction in Human Cell Research

Part of the book series: Current Human Cell Research and Applications ((CHCRA))

  • 617 Accesses

Abstract

The growth, survival, and metabolic activities of multicellular organisms at the cellular level are regulated not only by intracellular signal transduction pathways but also by systemic homeostasis and the pericellular microenvironment. The significance of the pericellular microenvironment is also established in tumorigenesis and malignant progression of transformed cells, in which processing of bioactive molecules by extracellular proteases has significant roles. Proteolytic activation of peptide growth factors in the pericellular microenvironment enables the induction of outside-in signaling in constituent cells in both physiological and pathological settings. This chapter will review the current knowledge of pericellular activation of peptide growth factors by serine proteases, with the main focus on activation of hepatocyte growth factor (HGF) that transduces signals through the MET receptor tyrosine kinase. There are two mechanisms for HGF activation in vivo: serum activation and cellular activation. Type II transmembrane serine proteases are membrane-anchored proteases that are part of cellular HGF-activating machinery. In the past decade, evidence for the roles of these proteases in cancer progression has been rapidly emerging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Shields MA, Dangi-Garimella S, Redig AJ, Munshi HG. Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochem J. 2012;441:541–52.

    Article  CAS  PubMed  Google Scholar 

  2. Koshikawa N, Mizushima H, Minegishi T, Eguchi F, Yotsumoto F, Nabeshima K, et al. Proteolytic activation of heparin-binding EGF-like growth factor by membrane-type matrix metalloproteinase-1 in ovarian carcinoma cells. Cancer Sci. 2011;102:111–6.

    Article  CAS  PubMed  Google Scholar 

  3. Taylor SR, Markesbery MG, Harding PA. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and proteolytic processing by a disintegrin and metalloproteinases (ADAM): a regulator of several pathways. Semin Cell Dev Biol. 2014;28:22–30.

    Article  CAS  PubMed  Google Scholar 

  4. Cataisson C, Michalowski AM, Shibuya K, Ryscavage A, Klosterman M, Wright L, et al. MET signaling in keratinocytes activates EGFR and initiates squamous carcinogenesis. Sci Signal. 2016;9(433):ra62.

    Article  PubMed  Google Scholar 

  5. Domoto T, Takino T, Guo L, Sato H. Cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase. Cancer Sci. 2012;103:448–54.

    Article  CAS  PubMed  Google Scholar 

  6. Shimomura T, Ochiai M, Kondo J, Morimoto Y. A novel protease obtained from FBS-containing culture supernatant, that processes single chain form hepatocyte growth factor to two chain form in serum-free culture. Cytotechnology. 1992;8:219–29.

    Article  CAS  PubMed  Google Scholar 

  7. Kataoka H, Miyata S, Uchinokura S, Itoh H. Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor. Cancer Metastasis Rev. 2003;22:223–36.

    Article  CAS  PubMed  Google Scholar 

  8. Miyazawa K, Shimomura T, Kitamura A, Kondo J, Morimoto Y, Kitamura N. Molecular cloning and sequence analysis of the cDNA for a human serine protease responsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. J Biol Chem. 1993;268:10024–8.

    CAS  PubMed  Google Scholar 

  9. Kataoka H, Kawaguchi M. Hepatocyte growth factor activator (HGFA): pathophysiological functions in vivo. FEBS J. 2010;277:2230–7.

    Article  CAS  PubMed  Google Scholar 

  10. Shimomura T, Kondo J, Ochiai M, Naka D, Miyazawa K, Morimoto Y, et al. Activation of the zymogen of hepatocyte growth factor activator by thrombin. J Biol Chem. 1993;268:22927–32.

    CAS  PubMed  Google Scholar 

  11. Itoh H, Naganuma S, Takeda N, Miyata S, Uchinokura S, Fukushima T, et al. Regeneration of injured intestinal mucosa is impaired in hepatocyte growth factor activator-deficient mice. Gastroenterology. 2004;127:1423–35.

    Article  CAS  PubMed  Google Scholar 

  12. Kawaguchi M, Orikawa H, Baba T, Fukushima T, Kataoka H. Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein. FEBS J. 2009;276:3481–90.

    Article  CAS  PubMed  Google Scholar 

  13. Li J, Chanda D, Shiri-Sverdlov R, Neumann D. MSP: an emerging player in metabolic syndrome. Cytokine Growth Factor Rev. 2015;26:75–82.

    Article  PubMed  Google Scholar 

  14. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21:309–22.

    Article  CAS  PubMed  Google Scholar 

  15. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12:89–103.

    Article  CAS  PubMed  Google Scholar 

  16. Vermeulen L, De Sousa E, Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 2010;12:468–76.

    Article  CAS  PubMed  Google Scholar 

  17. Lau EYT, Lo J, Cheng BYL, Ma MKF, Lee JMF, Ng JKY, et al. Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c-Met/FRA1/HEY1 signaling. Cell Rep. 2016;15:1175–89.

    Article  CAS  PubMed  Google Scholar 

  18. Antalis TM, Buzza MS, Hodge KM, Hooper JD, Netzel-Arnett S. The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment. Biochem J. 2010;428:325–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kawaguchi M, Kataoka H. Mechanisms of hepatocyte growth factor activation in cancer tissues. Cancers (Basel). 2014;6:1890–04.

    Article  CAS  Google Scholar 

  20. Tanabe LM, List K. The role of type II transmembrane serine protease mediated signaling in cancer. FEBS J. 2016. https://doi.org/10.1111/febs.13971.

  21. Yan W, Wu F, Morser J, Wu Q. Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Proc Natl Acad Sci U S A. 2000;97:8525–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miller GS, List K. The matriptase-prostasin proteolytic cascade in epithelial development and pathology. Cell Tissue Res. 2013;351:245–53.

    Article  CAS  PubMed  Google Scholar 

  23. Wang CY, Meynard D, Lin HY. The role of TMPRSS6/matriptase-2 in iron regulation and anemia. Front Pharmacol. 2014;5:114.

    PubMed  PubMed Central  Google Scholar 

  24. Dvorak HF. Tumors: wounds that do not heal. similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–9.

    Article  CAS  PubMed  Google Scholar 

  25. De Aberasturi AL, Calvo A. TMPRSS4: an emerging potential therapeutic target in cancer. Br J Cancer. 2015;112:4–8.

    Article  PubMed  Google Scholar 

  26. Cheng H, Fukushima T, Takahashi N, Tanaka H, Kataoka H. Hepatocyte growth factor activator inhibitor type 1 regulates epithelial to mesenchymal transition through membrane-bound serine proteinases. Cancer Res. 2009;69:1828–35.

    Article  CAS  PubMed  Google Scholar 

  27. Kataoka H, Hamasuna R, Itoh H, Kitamura N, Koono M. Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma. Cancer Res. 2000;60:6148–59.

    CAS  PubMed  Google Scholar 

  28. Szabo R, Rasmussen AL, Moyer AB, Kosa P, Schafer JM, Molinolo AA, et al. c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase. Oncogene. 2011;30:2003–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hashimoto T, Kato M, Shimomura T, Kitamura N. TMPRSS13, a type II transmembrane serine protease, is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro-hepatocyte growth factor. FEBS J. 2010;277:4888–900.

    Article  CAS  PubMed  Google Scholar 

  30. Kato M, Hashimoto T, Shimomura T, Kataoka H, Ohi H, Kitamura N. Hepatocyte growth factor activator inhibitor type 1 inhibits protease activity and proteolytic activation of human airway trypsin-like protease. J Biochem. 2012;151:179–87.

    Article  CAS  PubMed  Google Scholar 

  31. Bhatt AS, Welm A, Farady CJ, Vasquez M, Wilson K, Craik CS. Coordinate expression and functional profiling identify an extracellular proteolytic signaling pathway. Proc Natl Acad Sci U S A. 2007;104:5771–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ganesan R, Kolumam GA, Lin SJ, Xie M-H, Santell L, TD W, et al. Proteolytic activation of pro-macrophage-stimulating protein by hepsin. Mol Cancer Res. 2011;9:1175–86.

    Article  CAS  PubMed  Google Scholar 

  33. Orikawa H, Kawaguchi M, Baba T, Yorita K, Sakoda S, Kataoka H. Activation of macrophage-stimulating protein by human airway trypsin-like protease. FEBS Lett. 2012;586:217–21.

    Article  CAS  PubMed  Google Scholar 

  34. Lin CY, Wang JK, Torri J, Dou L, Sang QA, Dickson RB. Characterization of a novel, membrane-bound, 80-kDa matrix-degrading protease from human breast cancer cells. Monoclonal antibody production, isolation, and localization. J Biol Chem. 1997;272:9147–52.

    Article  CAS  PubMed  Google Scholar 

  35. Takeuchi T, Shuman MA, Craik CS. Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. Proc Natl Acad Sci U S A. 1999;96:11054–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Owen KA, Qiu D, Alves J, Schumacher AM, Kilpatrick LM, Li J, 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. 2010;426:219–28.

    Article  CAS  PubMed  Google Scholar 

  37. List K, Szabo R, Molinolo A, Sriuranpong V, Redeye V, Murdock T, et al. Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. Genes Dev. 2005;19:1934–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cheng MF, Huang MS, Lin CS, Lin LH, Lee HS, Jiang JC, Hsia KT. Expression of matriptase correlates with tumour progression and clinical prognosis in oral squamous cell carcinoma. Histopathology. 2014;65:24–34.

    Article  PubMed  Google Scholar 

  39. Zoratti GL, Tanabe LM, Hyland TE, Duhaime MJ, Colombo É, Leduc R, Marsault E, Johnson MD, Lin C-Y, Boerner J, Lang JE, List K. Matriptase regulates c-Met mediated proliferation and invasion in inflammatory breast cancer. Oncotarget. 2016;7:58162–73.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chou FP, Chen YW, Zhao XF, Xu-Monette ZY, Young KH, Gartenhaus RB, et al. Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas. Am J Pathol. 2013;183:1306–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Leytus SP, Loeb KR, Hagen FS, Kurachi K, Davie EW. A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. Biochemistry. 1988;27:1067–74.

    Article  CAS  PubMed  Google Scholar 

  42. Torres-Rosado A, O’Shea KS, Tsuji A, Chou SH, Kurachi K. Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. Proc Natl Acad Sci U S A. 1993;90:7181–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yu IS, Chen HJ, Lee YS, Huang PH, Lin SR, Tsai TW, et al. Mice deficient in hepsin, a serine protease, exhibit normal embryogenesis and unchanged hepatocyte regeneration ability. Thromb Haemost. 2000;84:865–70.

    CAS  PubMed  Google Scholar 

  44. Guipponi M, Tan J, Cannon PZF, Donley L, Crewther P, Clarke M, et al. Mice deficient for the type II transmembrane serine protease, TMPRSS1/hepsin, exhibit profound hearing loss. Am J Pathol. 2007;171:608–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Klezovitch O, Chevillet J, Mirosevich J, Roberts RL, Matusik RJ, Vasioukhin V. Hepsin promotes prostate cancer progression and metastasis. Cancer Cell. 2004;6:185–95.

    Article  CAS  PubMed  Google Scholar 

  46. Li W, Wang B-E, Moran P, Lipari T, Ganesan R, Corpuz R, et al. Pegylated kunitz domain inhibitor suppresses hepsin-mediated invasive tumor growth and metastasis. Cancer Res. 2009;69:8395–402.

    Article  CAS  PubMed  Google Scholar 

  47. Herter S, Piper DE, Aaron W, Gabriele T, Cutler G, Cao P, et al. Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. Biochem J. 2005;390:125–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Betsunoh H, Mukai S, Akiyama Y, Fukushima T, Minamiguchi N, Hasui Y, et al. Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma. Cancer Sci. 2007;98:491–8.

    Article  CAS  PubMed  Google Scholar 

  49. Hurst NJ, Najy AJ, Ustach CV, Movilla L, Kim H-RC. Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression. Biochem J. 2012;441:909–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ustach CV, Huang W, Conley-LaComb MK, Lin C-Y, Che M, Abrams J, et al. A novel signaling axis of matriptase/PDGF-D/ß-PDGFR in human prostate cancer. Cancer Res. 2010;70:9631–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Huang W, Kim H-RC. Dynamic regulation of platelet-derived growth factor D (PDGF-D) activity and extracellular spatial distribution by matriptase-mediated proteolysis. J Biol Chem. 2015;290:9162–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Najy AJ, Dyson G, Jena BP, Lin C-Y, Kim H-RC. Matriptase activation and shedding through PDGF-D-mediated extracellular acidosis. Am J Physiol Cell Physiol. 2016;310:C293–304.

    Article  PubMed  Google Scholar 

  53. Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, et al. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010;18:25–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Le Gall SM, Szabo R, Lee M, Kirchhofer D, Craik CS, Bugge TH, et al. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling. Blood. 2016;127:3260–9.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Kanemaru A, Yamamoto K, Kawaguchi M, Fukushima T, Lin C-Y, Johnson MD, et al. Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer-associated fibroblasts by paracrine activation of protease-activated receptor 2. Int J Cancer. 2017;140:130–41.

    Article  CAS  PubMed  Google Scholar 

  56. Kilpatrick LM, Harris RL, Owen KA, Bass R, Ghorayeb C, Bar-Or A, et al. Initiation of plasminogen activation on the surface of monocytes expressing the type II transmembrane serine protease matriptase. Blood. 2006;108:2616–23.

    Article  CAS  PubMed  Google Scholar 

  57. Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D. Pro-urokinase-type plasminogen activator is a substrate for hepsin. J Biol Chem. 2006;281:30439–46.

    Article  CAS  PubMed  Google Scholar 

  58. Shimomura T, Denda K, Kitamura A, Kawaguchi T, Kito M, Kondo J, et al. Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor. J Biol Chem. 1997;272:6370–6.

    Article  CAS  PubMed  Google Scholar 

  59. Kataoka H, Shimomura T, Kawaguchi T, Hamasuna R, Itoh H, Kitamura N, et al. Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA activity in the pericellular microenvironment. J Biol Chem. 2000;275:40453–62.

    Article  CAS  PubMed  Google Scholar 

  60. Kawaguchi T, Qin L, Shimomura T, Kondo J, Matsumoto K, Denda K, et al. Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor. J Biol Chem. 1997;272:27558–64.

    Article  CAS  PubMed  Google Scholar 

  61. Delaria KA, Muller DK, Marlor CW, Brown JE, Das RC, Roczniak SO, et al. Characterization of placental bikunin, a novel human serine protease inhibitor. J Biol Chem. 1997;272:12209–14.

    Article  CAS  PubMed  Google Scholar 

  62. Kataoka H, Suganuma T, Shimomura T, Itoh H, Kitamura N, Nabeshima K, et al. Distribution of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in human tissues. Cellular surface localization of HAI-1 in simple columnar epithelium and its modulated expression in injured and regenerative tissues. J Histochem Cytochem. 1999;47:673–82.

    Article  CAS  PubMed  Google Scholar 

  63. Kataoka H, Meng JY, Itoh H, Hamasuna R, Shimomura T, Suganuma T, et al. Localization of hepatocyte growth factor activator inhibitor type 1 in Langhans’ cells of human placenta. Histochem Cell Biol. 2000;114:469–75.

    CAS  PubMed  Google Scholar 

  64. Tanaka H, Nagaike K, Takeda N, Itoh H, Kohama K, Fukushima T, et al. Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is required for branching morphogenesis in the chorioallantoic placenta. Mol Cell Biol. 2005;25:5687–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mukai S, Fukushima T, Naka D, Tanaka H, Osada Y, Kataoka H. Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidases. FEBS J. 2008;275:1003–17.

    Article  CAS  PubMed  Google Scholar 

  66. Mukai S, Yorita K, Yamasaki K, Nagai T, Kamibeppu T, Sugie S, et al. Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis. Hum Cell. 2015;28:133–42.

    Article  CAS  PubMed  Google Scholar 

  67. Lin CY, Anders J, Johnson M, Dickson RB. Purification and characterization of a complex containing matriptase and a Kunitz-type serine protease inhibitor from human milk. J Biol Chem. 1999;274:18237–42.

    Article  CAS  PubMed  Google Scholar 

  68. Lai C-H, Lai Y-JJ, Chou F-P, Chang H-HD, Tseng C-C, Johnson MD, et al. Matriptase complexes and prostasin complexes with HAI-1 and HAI-2 in human milk: significant proteolysis in lactation. PLoS One. 2016;11:e0152904.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Kohama K, Kawaguchi M, Fukushima T, Lin C-Y, Kataoka H. Regulation of pericellular proteolysis by hepatocyte growth factor activator inhibitor type 1 (HAI-1) in trophoblast cells. Hum Cell. 2012;25:100–10.

    Article  CAS  PubMed  Google Scholar 

  70. Kawaguchi M, Kanemaru A, Sawaguchi A, Yamamoto K, Baba T, Lin C, et al. Hepatocyte growth factor activator inhibitor type 1 maintains the assembly of keratin into desmosomes in keratinocytes by regulating protease-activated receptor 2-dependent p38 signaling. Am J Pathol. 2015;185:1610–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Baba T, Kawaguchi M, Fukushima T, Sato Y, Orikawa H, Yorita K, et al. Loss of membrane-bound serine protease inhibitor HAI-1 induces oral squamous cell carcinoma cells’ invasiveness. J Pathol. 2012;228:181–92.

    Article  CAS  PubMed  Google Scholar 

  72. Fukushima T, Kawaguchi M, Yamasaki M, Tanaka H, Yorita K, Kataoka H. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells. Cancer Sci. 2011;102:407–13.

    Article  CAS  PubMed  Google Scholar 

  73. Ye J, Kawaguchi M, Haruyama Y, Kanemaru A, Fukushima T, Yamamoto K, et al. Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model. Cancer Sci. 2014;105:44–51.

    Article  CAS  PubMed  Google Scholar 

  74. Hoshiko S, Kawaguchi M, Fukushima T, Haruyama Y, Yorita K, Tanaka H, et al. Hepatocyte growth factor activator inhibitor type 1 is a suppressor of intestinal tumorigenesis. Cancer Res. 2013;73:2659–70.

    Article  CAS  PubMed  Google Scholar 

  75. Kawaguchi M, Yamamoto K, Kanemaru A, Tanaka H, Umezawa K, Fukushima T, et al. Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the ApcMin/+ mouse model. Oncotarget. 2016;7:68614–22.

    PubMed  PubMed Central  Google Scholar 

  76. Kataoka H, Uchino H, Denda K, Kitamura N, Itoh H, Tsubouchi H, et al. Evaluation of hepatocyte growth factor activator inhibitor expression in normal and malignant colonic mucosa. Cancer Lett. 1998;128:219–27.

    Article  CAS  PubMed  Google Scholar 

  77. Heinz-Erian P, Müller T, Krabichler B, Schranz M, Becker C, Rüschendorf F, et al. Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea. Am J Hum Genet. 2009;84:188–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Friis S, Sales KU, Schafer JM, Vogel LK, Kataoka H, Bugge TH. The protease inhibitor HAI-2, but not HAI-1, regulates matriptase activation and shedding through prostasin. J Biol Chem. 2014;289:22319–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Fukai K, Yokosuka O, Chiba T, Hirasawa Y, Tada M, Imazeki F, et al. Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma. Cancer Res. 2003;63:8674–9.

    CAS  PubMed  Google Scholar 

  80. Yamauchi M, Kataoka H, Itoh H, Seguchi T, Hasui Y, Osada Y. Hepatocyte growth factor activator inhibitor types 1 and 2 are expressed by tubular epithelium in kidney and down-regulated in renal cell carcinoma. J Urol. 2004;171:890–6.

    Article  CAS  PubMed  Google Scholar 

  81. Morris MR, Gentle D, Abdulrahman M, Clarke N, Brown M, Kishida T, et al. Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. Br J Cancer. 2008;98:496–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hamasuna R, Kataoka H, Meng JY, Itoh H, Moriyama T, Wakisaka S, et al. Reduced expression of hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) in human glioblastomas: implication for anti-invasive role of HAI-2/PB in glioblastoma cells. Int J Cancer. 2001;93:339–45.

    Article  CAS  PubMed  Google Scholar 

  83. Kongkham PN, Northcott PA, Ra YS, Nakahara Y, Mainprize TG, Croul SE, et al. An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res. 2008;68:9945–53.

    Article  CAS  PubMed  Google Scholar 

  84. Hwang S, Kim H-E, Min M, Raghunathan R, Panova IP, Munshi R, et al. Epigenetic silencing of SPINT2 promotes cancer cell motility via HGF-MET pathway activation in melanoma. J Invest Dermatol. 2015;135:2283–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Müller-Pillasch F, Wallrapp C, Bartels K, Varga G, Friess H, Büchler M, et al. Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer. Biochim Biophys Acta. 1998;1395:88–95.

    Article  PubMed  Google Scholar 

  86. Pereira MS, de Almeida GC, Pinto F, Viana-Pereira M, Reis RM. SPINT2 deregulation in prostate carcinoma. J Histochem Cytochem. 2016;64:32–41.

    Article  CAS  PubMed  Google Scholar 

  87. Tsai CH, Teng CH, YT T, Cheng TS, SR W, Ko CJ, et al. HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase. Oncogene. 2014;33:4643–52.

    Article  CAS  PubMed  Google Scholar 

  88. Ganesan R, Eigenbrot C, Kirchhofer D. Structural and mechanistic insight into how antibodies inhibit serine proteases. Biochem J. 2010;430:179–89.

    Article  CAS  PubMed  Google Scholar 

  89. Eigenbrot C, Ganesan R, Kirchhofer D. Hepatocyte growth factor activator (HGFA): molecular structure and interactions with HGFA inhibitor-1 (HAI-1). FEBS J. 2010;277:2215–22.

    Article  CAS  PubMed  Google Scholar 

  90. Han Z, Harris PKW, Karmakar P, Kim T, Owusu BY, Wildman SA, et al. α-Ketobenzothiazole serine protease inhibitors of aberrant HGF/c-MET and MSP/RON kinase pathway signaling in cancer. ChemMedChem. 2016;11:585–99.

    Article  CAS  PubMed  Google Scholar 

  91. Venukadasula PKM, Owusu BY, Bansal N, Ross LJ, Hobrath JV, Bao D, et al. Design and synthesis of nonpeptide inhibitors of hepatocyte growth factor activation. ACS Med Chem Lett. 2016;7:177–81.

    Article  CAS  PubMed  Google Scholar 

  92. Han Z, Harris PKW, Jones DE, Chugani R, Kim T, Agarwal M, et al. Inhibitors of HGFA, matriptase, and hepsin serine proteases: a nonkinase strategy to block cell signaling in cancer. ACS Med Chem Lett. 2014;5:1219–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Owusu BY, Bansal N, Venukadasula PKM, Ross LJ, Messick TE, Goel S, et al. Inhibition of pro-HGF activation by SRI31215, a novel approach to block oncogenic HGF/MET signaling. Oncotarget. 2016;7:29492–506.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of Interest

The authors declare no financial and commercial conflicts of interest.

Author information

Authors and Affiliations

  1. Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

    Hiroaki Kataoka & Tsuyoshi Fukushima

Authors
  1. Hiroaki Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsuyoshi Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroaki Kataoka .

Editor information

Editors and Affiliations

  1. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

    Nariyoshi Shinomiya

  2. Department of Pathology, University of Miyazaki, Miyazaki, Miyazaki, Japan

    Hiroaki Kataoka

  3. Department of Biomedical Sciences, Center of Excellence for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson, Tennessee, USA

    Qian Xie

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kataoka, H., Fukushima, T. (2018). Pericellular Activation of Peptide Growth Factors by Serine Proteases. In: Shinomiya, N., Kataoka, H., Xie, Q. (eds) Regulation of Signal Transduction in Human Cell Research. Current Human Cell Research and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-10-7296-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-7296-3_9

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-7295-6

  • Online ISBN: 978-981-10-7296-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation