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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Proteolytic cleavages of MET: the divide-and-conquer strategy of a receptor tyrosine kinase

  • Received : 2019.01.09
  • Published : 2019.04.30
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Abstract

Membrane-anchored full-length MET stimulated by its ligand HGF/SF induces various biological responses, including survival, growth, and invasion. This panel of responses, referred to invasive growth, is required for embryogenesis and tissue regeneration in adults. On the contrary, MET deregulation is associated with tumorigenesis in many kinds of cancer. In addition to its well-documented ligand-stimulated downstream signaling, the receptor can be cleaved by proteases such as secretases, caspases, and calpains. These cleavages are involved either in MET receptor inactivation or, more interestingly, in generating active fragments that can modify cell fate. For instance, MET fragments can promote cell death or invasion. Given a large number of proteases capable of cleaving MET, this receptor appears as a prototype of proteolytic-cleavage-regulated receptor tyrosine kinase. In this review, we describe and discuss the mechanisms and consequences, both physiological and pathological, of MET proteolytic cleavages.

Keywords

References

  1. Birchmeier C, Birchmeier W, Gherardi E and Vande Woude GF (2003) Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4, 915-925 https://doi.org/10.1038/nrm1261
  2. Bladt F, Riethmacher D, Isenmann S, Aguzzi A and Birchmeier C (1995) Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 376, 768-771 https://doi.org/10.1038/376768a0
  3. Schmidt C, Bladt F, Goedecke S et al (1995) Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699-702 https://doi.org/10.1038/373699a0
  4. Uehara Y, Minowa O, Mori C et al (1995) Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373, 702-705 https://doi.org/10.1038/373702a0
  5. Maina F, Hilton MC, Ponzetto C, Davies AM and Klein R (1997) Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons. Genes Dev 11, 3341-3350 https://doi.org/10.1101/gad.11.24.3341
  6. Chmielowiec J, Borowiak M, Morkel M et al (2007) c-Met is essential for wound healing in the skin. J Cell Biol 177, 151-162 https://doi.org/10.1083/jcb.200701086
  7. Borowiak M, Garratt AN, Wustefeld T, Strehle M, Trautwein C and Birchmeier C (2004) Met provides essential signals for liver regeneration. Proc Natl Acad Sci U S A 101, 10608-10613 https://doi.org/10.1073/pnas.0403412101
  8. Huh CG, Factor VM, Sanchez A, Uchida K, Conner EA and Thorgeirsson SS (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A 101, 4477-4482 https://doi.org/10.1073/pnas.0306068101
  9. Schiering N, Knapp S, Marconi M et al (2003) 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 U S A 100, 12654-12659 https://doi.org/10.1073/pnas.1734128100
  10. Longati P, Bardelli A, Ponzetto C, Naldini L and Comoglio PM (1994) Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET protooncogene (HGF receptor). Oncogene 9, 49-57
  11. Ponzetto C, Bardelli A, Zhen Z et al (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77, 261-271 https://doi.org/10.1016/0092-8674(94)90318-2
  12. Maina F, Casagranda F, Audero E et al (1996) Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development. Cell 87, 531-542 https://doi.org/10.1016/S0092-8674(00)81372-0
  13. Peschard P, Fournier TM, Lamorte L et al (2001) 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 https://doi.org/10.1016/S1097-2765(01)00378-1
  14. Hashigasako A, Machide M, Nakamura T and Matsumoto K (2004) Bi-directional regulation of Ser-985 phosphorylation of c-met via protein kinase C and protein phosphatase 2A involves c-Met activation and cellular responsiveness to hepatocyte growth factor. J Biol Chem 279, 26445-26452 https://doi.org/10.1074/jbc.M314254200
  15. Duplaquet L, Kherrouche Z, Baldacci S et al (2018) The multiple paths towards MET receptor addiction in cancer. Oncogene 37, 3200-3215 https://doi.org/10.1038/s41388-018-0185-4
  16. Olivero M, Rizzo M, Madeddu R et al (1996) Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br J Cancer 74, 1862-1868 https://doi.org/10.1038/bjc.1996.646
  17. Ichimura E, Maeshima A, Nakajima T and 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 https://doi.org/10.1111/j.1349-7006.1996.tb03111.x
  18. Wislez M, Rabbe N and Marchal J (2003) Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death. Cancer Res 63, 1405-1412
  19. Park S, Choi YL, Sung CO et al (2012) High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol 27, 197-207
  20. Koochekpour S, Jeffers M, Rulong S, et al (1997) Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 57, 5391-5398
  21. Ferracini R, Di Renzo MF, Scotlandi K et al (1995) The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 10, 739-749
  22. Tuck AB, Park M, Sterns EE, Boag A and Elliott BE (1996) Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. Am J Pathol 148, 225-232
  23. Ponzetto C, Giordano S, Peverali F et al (1991) c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene 6, 553-559
  24. Watermann I, Schmitt B and Stellmacher F (2015) Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation? Diagn Pathol 10, 130 https://doi.org/10.1186/s13000-015-0362-5
  25. Yang Y, Wu N, Shen J et al (2016) MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer. Gastric Cancer 19, 778-788 https://doi.org/10.1007/s10120-015-0545-5
  26. Sattler M, Reddy MM, Hasina R, Gangadhar T and Salgia R (2011) The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther Adv Med Oncol 3, 171-184 https://doi.org/10.1177/1758834011408636
  27. Krishnaswamy S, Kanteti R, Duke-Cohan JS et al (2009) Ethnic differences and functional analysis of MET mutations in lung cancer. Clin Cancer Res 15, 5714-5723 https://doi.org/10.1158/1078-0432.CCR-09-0070
  28. Baldacci S, Mazieres J, Tomasini P et al (2017) Outcome of EGFR-mutated NSCLC patients with MET-driven resistance to EGFR tyrosine kinase inhibitors. Oncotarget 8, 105103-105114 https://doi.org/10.18632/oncotarget.21707
  29. Prat M, Crepaldi T, Gandino L, Giordano S, Longati P and Comoglio P (1991) C-terminal truncated forms of Met, the hepatocyte growth factor receptor. Mol Cell Biol 11, 5954-5962 https://doi.org/10.1128/MCB.11.12.5954
  30. Galvani AP, Cristiani C, Carpinelli P, Landonio A and Bertolero F (1995) Suramin modulates cellular levels of hepatocyte growth factor receptor by inducing shedding of a soluble form. Biochem Pharmacol 50, 959-966 https://doi.org/10.1016/0006-2952(95)00219-P
  31. Jeffers M, Taylor GA, Weidner KM, Omura S and Vande-Woude GF (1997) Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway. Mol Cell Biol 17, 799-808 https://doi.org/10.1128/MCB.17.2.799
  32. Kopitz C, Gerg M, Bandapalli OR et al (2007) Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. Cancer Res 67, 8615-8623 https://doi.org/10.1158/0008-5472.CAN-07-0232
  33. Schelter F, Kobuch J, Moss ML et al (2010) A disintegrin and metalloproteinase-10 (ADAM-10) mediates DN30 antibody-induced shedding of the met surface receptor. J Biol Chem 285, 26335-26340 https://doi.org/10.1074/jbc.M110.106435
  34. Wajih N, Walter J and Sane DC (2002) Vascular origin of a soluble truncated form of the hepatocyte growth factor receptor (c-met). Circ Res 90, 46-52 https://doi.org/10.1161/hh0102.102756
  35. Foveau B, Ancot F and Leroy C (2009) Downregulation of the Met Receptor Tyrosine Kinase by Presenilindependent Regulated Intramembrane Proteolysis. Mol Biol Cell 20, 2494-2506
  36. Ancot F, Leroy C, Muharram G et al (2012) Shedding-Generated Met Receptor Fragments can be Routed to Either the Proteasomal or the Lysosomal Degradation Pathway. Traffic 13, 1261-1272 https://doi.org/10.1111/j.1600-0854.2012.01384.x
  37. Miller MA, Meyer AS and Beste MT (2013) ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling. Proc Natl Acad Sci U S A 110, E2074-2083 https://doi.org/10.1073/pnas.1222387110
  38. Trusolino L, Bertotti A and Comoglio PM (2010) MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 11, 834-848 https://doi.org/10.1038/nrm3012
  39. Copin MC, Lesaffre M, Berbon M et al (2016) High-MET status in non-small cell lung tumors correlates with receptor phosphorylation but not with the serum level of soluble form. Lung Cancer 101, 59-67 https://doi.org/10.1016/j.lungcan.2016.09.009
  40. McNeil BK, Sorbellini M and Grubb RL 3rd et al (2014) Preliminary evaluation of urinary soluble Met as a biomarker for urothelial carcinoma of the bladder. J Transl Med 12, 199 https://doi.org/10.1186/1479-5876-12-199
  41. Michieli P, Mazzone M, Basilico C et al (2004) Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 6, 61-73 https://doi.org/10.1016/j.ccr.2004.05.032
  42. Tulasne D, Deheuninck J, Lourenco FC et al (2004) Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage. Mol Cell Biol 24, 10328-10339 https://doi.org/10.1128/MCB.24.23.10328-10339.2004
  43. Lefebvre J, Muharram G, Leroy C et al (2013) Caspasegenerated fragment of the Met receptor favors apoptosis via the intrinsic pathway independently of its tyrosine kinase activity. Cell Death Dis 4, e871 https://doi.org/10.1038/cddis.2013.377
  44. Mebratu YA, Leyva-Baca I and Wathelet MG (2017) Bik reduces hyperplastic cells by increasing Bak and activating DAPk1 to juxtapose ER and mitochondria. Nat Commun 8, 803 https://doi.org/10.1038/s41467-017-00975-w
  45. Foveau B, Leroy C, Ancot F et al (2007) Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor. Cell Death Differ 14, 752-764 https://doi.org/10.1038/sj.cdd.4402080
  46. Ma J, Zou C and Guo L (2013) A novel death defying domain in met entraps the active site of caspase-3 and blocks apoptosis in hepatocytes. Hepatology 59, 2010-2021 https://doi.org/10.1002/hep.26769
  47. Furlan A and Tulasne D (2013) How does met regulate the survival/apoptosis balance? Hepatology 60, 1108-1109 https://doi.org/10.1002/hep.26969
  48. Peschard P, Ishiyama N, Lin T, Lipkowitz S and Park M (2004) A conserved DpYR motif in the juxtamembrane domain of the Met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation. J Biol Chem 279, 29565-29571 https://doi.org/10.1074/jbc.M403954200
  49. Deheuninck J, Goormachtigh G and Foveau B (2009) Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 inhibits its caspase-dependent cleavage. Cell Signal 21, 1455-1463 https://doi.org/10.1016/j.cellsig.2009.05.005
  50. Deheuninck J, Foveau B, Goormachtigh G et al (2008) Caspase cleavage of the MET receptor generates an HGF interfering fragment. Biochem Biophys Res Commun 367, 573-577 https://doi.org/10.1016/j.bbrc.2007.12.177
  51. Bredesen DE, Mehlen P and Rabizadeh S (2005) Receptors that mediate cellular dependence. Cell Death Differ 12, 1031-1043 https://doi.org/10.1038/sj.cdd.4401680
  52. Negulescu AM and Mehlen P (2018) Dependence receptors - the dark side awakens. FEBS J 285, 3909-3924 https://doi.org/10.1111/febs.14507
  53. Ichim G, Genevois AL, Menard M et al (2013) The Dependence Receptor TrkC Triggers Mitochondria-Dependent Apoptosis upon Cobra-1 Recruitment. Mol Cell 51, 632-646 https://doi.org/10.1016/j.molcel.2013.08.021
  54. Menard M, Costechareyre C, Ichim G et al (2018) Hey1-and p53-dependent TrkC proapoptotic activity controls neuroblastoma growth. PLoS Biol 16, e2002912 https://doi.org/10.1371/journal.pbio.2002912
  55. Halestrap AP (2010) A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection. Biochem Soc Trans 38, 841-860 https://doi.org/10.1042/BST0380841
  56. Francis RJ, Kotecha S and Hallett MB (2013) $Ca^{2+}$ activation of cytosolic calpain induces the transition from apoptosis to necrosis in neutrophils with externalized phosphatidylserine. J Leukoc Biol 93, 95-100 https://doi.org/10.1189/jlb.0412212
  57. Yun B, Lee H, Ghosh M et al (2014) Serine hydrolase inhibitors block necrotic cell death by preventing calcium overload of the mitochondria and permeability transition pore formation. J Biol Chem 289, 1491-1504 https://doi.org/10.1074/jbc.M113.497651
  58. Montagne R, Berbon M, Doublet L et al (2015) Necrosisand apoptosis-related Met cleavages have divergent functional consequences. Cell Death Dis 6, e1769 https://doi.org/10.1038/cddis.2015.132
  59. Billger M, Wallin M and Karlsson JO (1988) Proteolysis of tubulin and microtubule-associated proteins 1 and 2 by calpain I and II. Difference in sensitivity of assembled and disassembled microtubules. Cell Calcium 9, 33-44 https://doi.org/10.1016/0143-4160(88)90036-X
  60. Czogalla A and Sikorski AF (2005) Spectrin and calpain: a 'target' and a 'sniper' in the pathology of neuronal cells. Cell Mol Life Sci 62, 1913-1924 https://doi.org/10.1007/s00018-005-5097-0
  61. Kelly BL, Vassar R and Ferreira A (2005) Beta-amyloidinduced dynamin 1 depletion in hippocampal neurons. A potential mechanism for early cognitive decline in Alzheimer disease. J Biol Chem 280, 31746-31753 https://doi.org/10.1074/jbc.M503259200
  62. Cortot AB, Kherrouche Z, Descarpentries C et al (2017) Exon 14 deleted MET receptor as a new biomarker and target in cancers. J Natl Cancer Inst 109
  63. Lee JH, Han SU, Cho H et al (2009) A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19, 4947-4953 https://doi.org/10.1038/sj/onc/1203874
  64. Ma PC, Kijima T, Maulik G et al (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63, 6272-6281
  65. Tyner JW, Fletcher LB, Wang EQ et al (2010) MET receptor sequence variants R970C and T992I lack transforming capacity. Cancer Res 70, 6233-6237 https://doi.org/10.1158/0008-5472.CAN-10-0429
  66. Shieh JM, Tang YA, Yang TH et al (2013) Lack of association of C-Met-N375S sequence variant with lung cancer susceptibility and prognosis. Int J Med Sci 10, 988-994 https://doi.org/10.7150/ijms.5944
  67. Boland JM, Jang JS, Li J et al (2013) MET and EGFR mutations identified in ALK-rearranged pulmonary adenocarcinoma: molecular analysis of 25 ALK-positive cases. J Thorac Oncol 8, 574-581 https://doi.org/10.1097/JTO.0b013e318287c395
  68. Zaffaroni D, Spinola M, Galvan A et al (2005) Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis. Oncogene 24, 1084-1090 https://doi.org/10.1038/sj.onc.1208324
  69. Montagne R, Baranzelli A, Muharram G et al (2017) MET receptor variant R970C favors calpain-dependent generation of a fragment promoting epithelial cell scattering. Oncotarget 8, 11268-11283 https://doi.org/10.18632/oncotarget.14499
  70. Merilahti JAM and Elenius K (2019) Gamma-secretasedependent signaling of receptor tyrosine kinases. Oncogene 38, 151-163 https://doi.org/10.1038/s41388-018-0465-z
  71. Matteucci E, Bendinelli P and Desiderio MA (2009) Nuclear localization of active HGF receptor Met in aggressive MDA-MB231 breast carcinoma cells. Carcinogenesis 30, 937-945 https://doi.org/10.1093/carcin/bgp080
  72. Chaudhary SC, Cho MG, Nguyen TT, Park KS, Kwon MH and Lee JH (2014) A putative pH-dependent nuclear localization signal in the juxtamembrane region of c-Met. Exp Mol Med 46, e119 https://doi.org/10.1038/emm.2014.67
  73. Tauszig-Delamasure S, Yu LY, Cabrera JR et al (2007) The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm. Proc Natl Acad Sci U S A 104, 13361-13366 https://doi.org/10.1073/pnas.0701243104
  74. Bordeaux MC, Forcet C, Granger L et al (2000) The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease. EMBO J 19, 4056-4063 https://doi.org/10.1093/emboj/19.15.4056
  75. Wang H, Boussouar A, Mazelin L et al (2018) The Proto-oncogene c-Kit Inhibits Tumor Growth by Behaving as a Dependence Receptor. Mol Cell 72, 413-425 e415 https://doi.org/10.1016/j.molcel.2018.08.040
  76. Genevois AL, Ichim G, Coissieux MM et al (2013) Dependence receptor TrkC is a putative colon cancer tumor suppressor. Proc Natl Acad Sci U S A 110, 3017-3022 https://doi.org/10.1073/pnas.1212333110
  77. Luo Y, Kaz AM, Kanngurn S et al (2013) NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer. PLoS Genet 9, e1003552 https://doi.org/10.1371/journal.pgen.1003552
  78. De Oliveira AT, Matos D, Logullo AF et al (2009) MET Is highly expressed in advanced stages of colorectal cancer and indicates worse prognosis and mortality. Anticancer Res 29, 4807-4811
  79. Petrelli A, Circosta P, Granziero L et al (2006) Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity. Proc Natl Acad Sci U S A 103, 5090-5095 https://doi.org/10.1073/pnas.0508156103
  80. Pacchiana G, Chiriaco C, Stella MC et al (2010) Monovalency unleashes the full therapeutic potential of the DN-30 anti-Met antibody. J Biol Chem 285, 36149-36157 https://doi.org/10.1074/jbc.M110.134031
  81. Cignetto S, Modica C, Chiriaco C et al (2016) Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody. Mol Oncol 10, 938-948 https://doi.org/10.1016/j.molonc.2016.03.004
  82. Vigna E, Chiriaco C, Cignetto S et al (2015) Inhibition of ligand-independent constitutive activation of the Met oncogenic receptor by the engineered chemically-modified antibody DN30. Mol Oncol 9, 1760-1772 https://doi.org/10.1016/j.molonc.2015.05.007
  83. Vigna E, Pacchiana G, Chiriaco C et al (2014) Targeted therapy by gene transfer of a monovalent antibody fragment against the Met oncogenic receptor. J Mol Med (Berl) 92, 65-76 https://doi.org/10.1007/s00109-013-1079-0
  84. Basilico C, Modica C, Maione F, Vigna E and Comoglio PM (2018) Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy. Int J Cancer [Epub ahead of print]
  85. Perk LR, Stigter-van Walsum M, Visser GW et al (2008) Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30. Eur J Nucl Med Mol Imaging 35, 1857-1867 https://doi.org/10.1007/s00259-008-0774-5
  86. Athauda G, Giubellino A, Coleman JA et al (2006) c-Met ectodomain shedding rate correlates with malignant potential. Clin Cancer Res 12(14 Pt 1), 4154-4162 https://doi.org/10.1158/1078-0432.CCR-06-0250
  87. Fu L, Guo W, Liu B et al (2013) Shedding of c-Met ectodomain correlates with c-Met expression in non-small cell lung cancer. Biomarkers 18, 126-135 https://doi.org/10.3109/1354750X.2012.751455
  88. Lv H, Shan B, Tian Z, Li Y, Zhang Y and Wen S (2015) Soluble c-Met is a reliable and sensitive marker to detect c-Met expression level in lung cancer. Biomed Res Int 2015, 626578 https://doi.org/10.1155/2015/626578
  89. Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043 https://doi.org/10.1126/science.1141478
  90. Siebel C and Lendahl U (2017) Notch Signaling in Development, Tissue Homeostasis, and Disease. Physiol Rev 97, 1235-1294 https://doi.org/10.1152/physrev.00005.2017