The Urokinase Plasminogen Activation System in Pancreatic Cancer: Prospective Diagnostic and Therapeutic Targets.
metastasis
pancreatic cancer
pancreatic ductal adenocarcinoma (PDAC)
plasmin
plasminogen activator inhibitor
plasminogen receptors
serine proteases
tumour microenvironment
urokinase plasminogen activator (uPA)
urokinase plasminogen activator receptor (uPAR)
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
18 01 2022
18 01 2022
Historique:
received:
14
12
2021
revised:
13
01
2022
accepted:
16
01
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Pancreatic cancer is a highly aggressive malignancy that features high recurrence rates and the poorest prognosis of all solid cancers. The urokinase plasminogen activation system (uPAS) is strongly implicated in the pathophysiology and clinical outcomes of patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic cancers. Overexpression of the urokinase-type plasminogen activator (uPA) or its cell surface receptor uPAR is a key step in the acquisition of a metastatic phenotype via multiple mechanisms, including the increased activation of cell surface localised plasminogen which generates the serine protease plasmin. This triggers multiple downstream processes that promote tumour cell migration and invasion. Increasing clinical evidence shows that the overexpression of uPA, uPAR, or of both is strongly associated with worse clinicopathological features and poor prognosis in PDAC patients. This review provides an overview of the current understanding of the uPAS in the pathogenesis and progression of pancreatic cancer, with a focus on PDAC, and summarises the substantial body of evidence that supports the role of uPAS components, including plasminogen receptors, in this disease. The review further outlines the clinical utility of uPAS components as prospective diagnostic and prognostic biomarkers for PDAC, as well as a rationale for the development of novel uPAS-targeted therapeutics.
Identifiants
pubmed: 35204653
pii: biom12020152
doi: 10.3390/biom12020152
pmc: PMC8961517
pii:
doi:
Substances chimiques
Plasminogen
9001-91-6
Urokinase-Type Plasminogen Activator
EC 3.4.21.73
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Cancer Res. 1994 Sep 1;54(17):4671-5
pubmed: 8062262
Clin Chim Acta. 2000 Feb 15;291(2):113-35
pubmed: 10675719
Cancer Res. 1985 Apr;45(4):1787-96
pubmed: 3884145
Biomed Pharmacother. 2018 Feb;98:886-898
pubmed: 29571259
Nat Rev Cancer. 2008 Jul;8(7):535-45
pubmed: 18548086
J Biomed Sci. 2019 Oct 20;26(1):78
pubmed: 31629410
N Engl J Med. 2011 Aug 4;365(5):395-409
pubmed: 21714641
J Surg Oncol. 2010 Sep 1;102(3):235-41
pubmed: 20740581
Gastroenterology. 2019 May;156(7):2024-2040
pubmed: 30721664
Carcinogenesis. 1993 Dec;14(12):2575-9
pubmed: 8269629
JAMA. 2013 Oct 9;310(14):1473-81
pubmed: 24104372
Theranostics. 2015 Sep 13;5(12):1303-16
pubmed: 26516369
Chin Med J (Engl). 2018 Dec 20;131(24):2947-2952
pubmed: 30539907
J Biol Chem. 1994 Apr 1;269(13):9416-9
pubmed: 8144524
Cancer Microenviron. 2011 Aug;4(2):199-208
pubmed: 21909879
J Proteome Res. 2009 Apr;8(4):1647-56
pubmed: 19714807
Int J Cancer. 1998 Oct 23;79(5):449-54
pubmed: 9761111
J Biol Chem. 1992 Feb 25;267(6):3878-85
pubmed: 1310986
PLoS One. 2013;8(1):e53532
pubmed: 23341946
J Cell Biol. 1985 Nov;101(5 Pt 1):1826-41
pubmed: 2414304
Oncotarget. 2017 Nov 15;8(63):106405-106414
pubmed: 29290958
Cancer Res. 2021 May 1;81(9):2259-2269
pubmed: 33509939
Cancer Res. 1998 May 1;58(9):1843-9
pubmed: 9581823
Clin Cancer Res. 2020 Jul 15;26(14):3608-3615
pubmed: 32341034
Int J Cancer. 2001 May 15;92(4):497-502
pubmed: 11304683
Br J Cancer. 1998 Sep;78(6):833-9
pubmed: 9743310
Nat Struct Mol Biol. 2008 Apr;15(4):422-3
pubmed: 18376415
Biochem J. 2007 Dec 1;408(2):203-10
pubmed: 17696882
BMC Cancer. 2021 Sep 16;21(1):1039
pubmed: 34530774
Blood. 2011 Nov 3;118(18):4789-97
pubmed: 21908427
J Cell Mol Med. 2021 Mar;25(6):3006-3018
pubmed: 33580614
Curr Pharm Des. 2003;9(19):1483-98
pubmed: 12871064
Oncotarget. 2015 Mar 10;6(7):4553-61
pubmed: 25714017
Int J Mol Sci. 2021 Mar 15;22(6):
pubmed: 33804289
Oncotarget. 2016 Feb 2;7(5):5598-612
pubmed: 26734996
Br J Cancer. 2009 Oct 20;101(8):1298-306
pubmed: 19755983
J Hematol Oncol. 2017 Jan 13;10(1):16
pubmed: 28086938
J Exp Med. 2003 Sep 15;198(6):863-8
pubmed: 12963694
J Biol Chem. 2007 May 4;282(18):13561-72
pubmed: 17355965
World J Oncol. 2019 Feb;10(1):10-27
pubmed: 30834048
Nucl Med Biol. 2013 Jul;40(5):618-24
pubmed: 23602763
Sci Rep. 2020 Jun 1;10(1):8820
pubmed: 32483216
Int J Oncol. 2006 Feb;28(2):369-74
pubmed: 16391791
Mod Pathol. 2003 May;16(5):403-10
pubmed: 12748245
Br J Cancer. 2009 Oct 6;101(7):1145-54
pubmed: 19724273
BMC Cancer. 2008 Jul 10;8:194
pubmed: 18616803
Eur J Biochem. 1994 Jan 15;219(1-2):455-62
pubmed: 8307012
BMC Cancer. 2017 May 19;17(1):350
pubmed: 28526008
J Mol Med (Berl). 2006 Dec;84(12):1015-22
pubmed: 17039343
Pancreatology. 2012 Mar-Apr;12(2):130-40
pubmed: 22487523
J Urol. 1989 Jul;142(1):193-8
pubmed: 2659823
Pancreas. 2002 Aug;25(2):e30-5
pubmed: 12142752
Cancer Res. 1994 Aug 1;54(15):4065-71
pubmed: 8033138
Blood. 1992 Mar 1;79(5):1178-84
pubmed: 1536945
World J Gastroenterol. 2009 Dec 21;15(47):5898-906
pubmed: 20014453
J Clin Med. 2021 Feb 03;10(4):
pubmed: 33546207
Radiat Oncol. 2019 Aug 8;14(1):141
pubmed: 31395068
Structure. 1995 Jul 15;3(7):681-91
pubmed: 8591045
Annu Rev Cell Dev Biol. 2011;27:441-64
pubmed: 21985671
Clin Cancer Res. 2001 Aug;7(8):2396-404
pubmed: 11489818
Lancet Oncol. 2014 Oct;15(11):e484-92
pubmed: 25281467
Tumour Biol. 2008;29(1):57-62
pubmed: 18497550
Br J Cancer. 1998 May;77(10):1586-97
pubmed: 9635833
Breast Cancer Res. 2014 Aug 22;16(4):428
pubmed: 25677449
Biomark Insights. 2017 Jun 22;12:1177271917715443
pubmed: 28690396
Cancer Res. 2004 Jan 1;64(1):286-91
pubmed: 14729636
Blood. 2007 Nov 15;110(10):3763-72
pubmed: 17690254
Cancer Metastasis Rev. 2006 Mar;25(1):9-34
pubmed: 16680569
Oncogene. 2017 Jul 27;36(30):4288-4298
pubmed: 28346421
Cancers (Basel). 2020 Jun 01;12(6):
pubmed: 32492943
Ann Surg. 2013 Jan;257(1):17-26
pubmed: 22895395
J Protein Chem. 1998 Nov;17(8):845-54
pubmed: 9988531
Pancreas. 2018 Jul;47(6):675-689
pubmed: 29894417
Cancer Manag Res. 2018 Nov 15;10:5735-5745
pubmed: 30532594
J Cell Biol. 1992 Jun;117(5):1101-7
pubmed: 1374415
Cancer Res. 2010 Jun 15;70(12):5136-46
pubmed: 20501830
Front Genet. 2021 Jan 28;11:614726
pubmed: 33584813
Cancer Metastasis Rev. 2019 Sep;38(3):357-387
pubmed: 31529338
Am J Gastroenterol. 1993 Nov;88(11):1928-33
pubmed: 8237943
Nat Rev Mol Cell Biol. 2010 Jan;11(1):23-36
pubmed: 20027185
World J Surg. 2007 Mar;31(3):493-502; discussion 503
pubmed: 17219285
BMC Cancer. 2014 May 03;14:310
pubmed: 24885595
Clin Cancer Res. 1995 Oct;1(10):1079-87
pubmed: 9815897
Ann Surg Oncol. 2012 Jan;19(1):169-75
pubmed: 21761104
Cancer Epidemiol Biomarkers Prev. 1995 Dec;4(8):871-6
pubmed: 8634660
ISRN Dermatol. 2013 Jul 18;2013:597927
pubmed: 23984088
Oncotarget. 2017 Apr 4;8(14):23099-23109
pubmed: 28416743
J Biol Chem. 1988 Aug 25;263(24):11928-34
pubmed: 3403557
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
J Clin Invest. 1991 Oct;88(4):1067-72
pubmed: 1833420
Gastroenterol Res Pract. 2018 Feb 1;2018:3842198
pubmed: 29483925
FEBS J. 2011 Apr;278(7):1064-74
pubmed: 21261815
Eur J Biochem. 1995 Jan 15;227(1-2):407-15
pubmed: 7851415
Semin Thromb Hemost. 1991 Jul;17(3):175-82
pubmed: 1839079
Front Cell Dev Biol. 2021 Jan 11;8:607209
pubmed: 33505964
Cell Mol Life Sci. 2000 Jan 20;57(1):25-40
pubmed: 10949579
Breast Cancer Res. 2007;9(1):R14
pubmed: 17257442
Anticancer Res. 2005 Jan-Feb;25(1A):79-83
pubmed: 15816522
Virchows Arch. 2008 Mar;452(3):241-50
pubmed: 18236071
Blood Coagul Fibrinolysis. 1992 Oct;3(5):605-14
pubmed: 1333289
Front Biosci. 2008 May 01;13:5441-61
pubmed: 18508598
J Biol Chem. 1985 Apr 10;260(7):4303-11
pubmed: 3920216
J Proteome Res. 2011 Jan 7;10(1):105-12
pubmed: 20455595
Structure. 2000 May 15;8(5):553-63
pubmed: 10801494
Cancers (Basel). 2017 Nov 16;9(11):
pubmed: 29144412
J Biol Chem. 1994 Dec 23;269(51):32380-8
pubmed: 7528215
Cell Adh Migr. 2012 Nov-Dec;6(6):535-615
pubmed: 23076133
Expert Rev Anticancer Ther. 2010 Oct;10(10):1647-61
pubmed: 20942635
World J Surg. 1997 Feb;21(2):195-200
pubmed: 8995078
J Cell Biol. 2007 Jun 4;177(5):927-39
pubmed: 17548516
Semin Thromb Hemost. 2013 Jun;39(4):329-37
pubmed: 23532575
Cancer Sci. 2003 Jan;94(1):43-9
pubmed: 12708473
FEBS Lett. 1992 Feb 3;297(1-2):112-8
pubmed: 1551416
N Engl J Med. 2020 Feb 6;382(6):503-513
pubmed: 31995683
J Clin Invest. 1999 Jun;103(11):1587-95
pubmed: 10359568
J Biol Chem. 1996 Oct 11;271(41):25684-91
pubmed: 8810346
J Biol Chem. 1987 Apr 5;262(10):4437-40
pubmed: 3031025
J Nucl Med. 2012 Jan;53(1):138-45
pubmed: 22213823
Int J Cancer. 1996 Dec 20;69(6):475-9
pubmed: 8980250
Nature. 1983 Jan 6;301(5895):89-92
pubmed: 6185846
J Clin Invest. 1988 Dec;82(6):1948-55
pubmed: 2974046
Cancer Res. 2014 Jun 1;74(11):2913-21
pubmed: 24840647
Saudi J Gastroenterol. 2012 Mar-Apr;18(2):118-21
pubmed: 22421717
Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2002 Nov;16(11):599-602
pubmed: 15515548
J Cancer Metastasis Treat. 2020;6:
pubmed: 37822969
Int J Mol Sci. 2014 Nov 17;15(11):21229-52
pubmed: 25407528
Mol Biol Cell. 2001 Apr;12(4):863-79
pubmed: 11294892
Oncotarget. 2019 Oct 29;10(59):6308-6316
pubmed: 31695839
J Biol Chem. 1991 Jul 5;266(19):12752-8
pubmed: 1829461
Epigenomics. 2009 Dec;1(2):239-59
pubmed: 20495664
Gut. 2004 Jul;53(7):993-1000
pubmed: 15194650
J Invest Dermatol. 2001 Mar;116(3):353-8
pubmed: 11231307
Clin Physiol Funct Imaging. 2013 Sep;33(5):329-37
pubmed: 23701192
Cancer Res. 2009 Dec 1;69(23):8853-61
pubmed: 19920204
Nat Commun. 2020 Jun 24;11(1):3175
pubmed: 32581250
Therap Adv Gastroenterol. 2013 Jul;6(4):321-37
pubmed: 23814611
J Biol Chem. 2004 Aug 6;279(32):33613-22
pubmed: 15150279
Bioorg Med Chem. 2021 May 1;37:116116
pubmed: 33799173
Pancreas. 2008 Mar;36(2):160-7
pubmed: 18376307
Br J Cancer. 2005 Oct 3;93(7):799-803
pubmed: 16091756
Oncotarget. 2016 Nov 8;7(45):73912-73924
pubmed: 27729618
Pac Symp Biocomput. 2021;26:297-308
pubmed: 33691026
J Immunol. 2012 Jul 1;189(1):365-72
pubmed: 22623332
Dig Dis. 2019;37(4):315-324
pubmed: 30699408
Neoplasia. 2002 May-Jun;4(3):204-17
pubmed: 11988840
Am J Respir Cell Mol Biol. 2006 Dec;35(6):705-13
pubmed: 16840775
Ann Surg Oncol. 2008 Nov;15(11):3157-68
pubmed: 18712570
Clin Cancer Res. 2001 Jun;7(6):1743-9
pubmed: 11410515
Biochemistry. 1998 Dec 1;37(48):16958-66
pubmed: 9836589
Nat Chem Biol. 2021 Jul;17(7):776-783
pubmed: 33859413
Gut. 2016 Sep;65(9):1505-13
pubmed: 25986944
J Gastrointest Oncol. 2012 Jun;3(2):105-19
pubmed: 22811878
Biomed Res Int. 2014;2014:625176
pubmed: 24967388
Exp Hematol Oncol. 2013 Apr 17;2(1):12
pubmed: 23594883
Int J Cancer. 2009 Aug 1;125(3):639-48
pubmed: 19425054
Nat Rev Gastroenterol Hepatol. 2009 Jul;6(7):412-22
pubmed: 19506583
J Biol Chem. 1998 Feb 20;273(8):4790-9
pubmed: 9468544
J Physiol Pharmacol. 2016 Feb;67(1):93-101
pubmed: 27010898
Biochemistry. 2006 Aug 8;45(31):9463-74
pubmed: 16878981
Cancer Metastasis Rev. 2019 Sep;38(3):483-492
pubmed: 31734763
Oncotarget. 2015 May 10;6(13):11098-113
pubmed: 25860938
World J Gastroenterol. 2014 Jun 28;20(24):7864-77
pubmed: 24976723
J Cell Sci. 1995 Mar;108 ( Pt 3):1071-82
pubmed: 7542667
Exp Cell Res. 1993 Sep;208(1):197-208
pubmed: 8359216
Sci Rep. 2020 Oct 2;10(1):16425
pubmed: 33009477
Int J Oncol. 2018 Jan;52(1):5-18
pubmed: 29115416
Theranostics. 2020 Mar 4;10(9):4116-4133
pubmed: 32226543
PLoS One. 2011 Apr 29;6(4):e19390
pubmed: 21572519
Eur Urol. 2012 Nov;62(5):745-52
pubmed: 22704366
Blood. 2010 Aug 19;116(7):1136-46
pubmed: 20424186
FEBS J. 2010 Jan;277(1):2-21
pubmed: 19843174
J Biol Chem. 1986 Sep 5;261(25):11656-62
pubmed: 3745161
Cancer Res. 2003 Apr 1;63(7):1684-95
pubmed: 12670923
J Biol Chem. 1986 Mar 15;261(8):3486-9
pubmed: 3081506
Sci Rep. 2020 Jan 28;10(1):1332
pubmed: 31992753
J Nucl Med. 2017 Mar;58(3):379-386
pubmed: 27609788
Mol Carcinog. 2000 Jan;27(1):10-7
pubmed: 10642432
Clin Cancer Res. 2003 Oct 15;9(13):4935-43
pubmed: 14581368
Biochim Biophys Acta. 1993 Jan 15;1161(1):105-12
pubmed: 8422417
Int J Cancer. 2012 Aug 15;131(4):E329-36
pubmed: 21901747
Clin Endosc. 2012 Jun;45(2):115-6
pubmed: 22866249
Blood. 2010 Feb 18;115(7):1319-30
pubmed: 19897580
J Med Chem. 2018 Sep 27;61(18):8299-8320
pubmed: 30130401
Lung Cancer. 2002 Oct;38(1):31-8
pubmed: 12367790
Cancers (Basel). 2011 Apr 01;3(2):1821-43
pubmed: 24212784
Carcinogenesis. 2019 Aug 22;40(8):947-955
pubmed: 30805627
Nat Rev Gastroenterol Hepatol. 2018 Jun;15(6):333-348
pubmed: 29717230
Ann Surg Treat Res. 2018 May;94(5):247-253
pubmed: 29732356
J Natl Cancer Inst. 2002 Jan 16;94(2):116-28
pubmed: 11792750
Clin Cancer Res. 2014 Mar 15;20(6):1477-88
pubmed: 24452790
Int J Mol Sci. 2013 Mar 19;14(3):6259-305
pubmed: 23519104
World J Gastroenterol. 2018 Nov 21;24(43):4846-4861
pubmed: 30487695
Arch Biochem Biophys. 1991 May 1;286(2):625-8
pubmed: 1654795
Int J Cancer. 2002 Jan 20;97(3):379-85
pubmed: 11774293
Zhonghua Gan Zang Bing Za Zhi. 2019 Jul 20;27(7):505-510
pubmed: 31357775
Clin Cancer Res. 2007 Jun 1;13(11):3115-24
pubmed: 17545513
Hum Pathol. 1995 Oct;26(10):1133-8
pubmed: 7557947
Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):1104-17
pubmed: 11451738
Clin Cancer Res. 1996 Apr;2(4):613-8
pubmed: 9816210
BMC Cancer. 2011 Oct 14;11:448
pubmed: 21999221
Am J Pathol. 2009 Jun;174(6):2246-53
pubmed: 19435784
Br J Cancer. 1997;76(5):622-7
pubmed: 9303361
Biophys Rev. 2022 Jan 6;14(1):277-301
pubmed: 35340592
Dig Dis Sci. 1988 Oct;33(10):1223-5
pubmed: 3168694
Br J Cancer. 1997;75(3):388-95
pubmed: 9020484
Int J Cancer. 2007 Apr 1;120(7):1511-7
pubmed: 17192896
Comb Chem High Throughput Screen. 2009 Dec;12(10):961-7
pubmed: 20025562
Genome Biol. 2006;7(5):216
pubmed: 16737556
N Engl J Med. 2014 Apr 3;370(14):1298-306
pubmed: 24693890
Cancer Cell. 2017 Jan 9;31(1):5-19
pubmed: 28073003
Gut. 2011 Jun;60(6):861-8
pubmed: 20966025
Front Oncol. 2020 Apr 15;10:397
pubmed: 32351878
Int J Med Sci. 2017 Jun 22;14(7):655-661
pubmed: 28824297
Front Oncol. 2021 Feb 10;10:593706
pubmed: 33643901
JAMA Surg. 2018 Dec 1;153(12):e183617
pubmed: 30285076
BMC Med. 2018 Aug 21;16(1):125
pubmed: 30126408
Ann Surg Oncol. 2018 Nov;25(12):3483-3491
pubmed: 29786131
Thromb Haemost. 1987 Oct 28;58(3):936-42
pubmed: 2829380
Oncogene. 1998 Feb 5;16(5):625-33
pubmed: 9482108
J Cell Biochem. 2008 Oct 1;105(2):370-80
pubmed: 18636554
Radiology. 2011 Sep;260(3):658-63
pubmed: 21712474
Clin Exp Metastasis. 2000;18(2):171-8
pubmed: 11235993
J Biol Chem. 2004 Apr 23;279(17):18063-72
pubmed: 14769799
J Biol Chem. 1991 Jul 5;266(19):12329-36
pubmed: 1712017
Mol Cancer Res. 2011 Apr;9(4):377-89
pubmed: 21389187
Cells. 2018 Oct 05;7(10):
pubmed: 30301152
Adv Biol Regul. 2018 May;68:77-87
pubmed: 29221990
Curr Pharm Des. 2007;13(35):3568-75
pubmed: 18220793
Oncotarget. 2020 Sep 22;11(38):3489-3501
pubmed: 33014285
Front Biosci. 2001 Nov 01;6:D1403-11
pubmed: 11689350
J Biol Chem. 1988 Aug 15;263(23):11189-95
pubmed: 2969891
Hepatogastroenterology. 2011 Nov-Dec;58(112):1918-25
pubmed: 22234062
J Gastroenterol Hepatol. 2005 Feb;20(2):256-63
pubmed: 15683429
Clin Cancer Res. 1999 Aug;5(8):2094-102
pubmed: 10473092
Cell Rep. 2012 Mar 29;1(3):185-90
pubmed: 22832192
Front Biosci. 2003 May 01;8:s294-304
pubmed: 12700073
BMC Cancer. 2006 Jan 13;6:10
pubmed: 16412231
Scand J Gastroenterol. 2021 Jan;56(1):81-85
pubmed: 33245246
Bioorg Med Chem Lett. 2019 Dec 15;29(24):126753
pubmed: 31679971
Gastroenterology. 2013 May;144(5):1098-106
pubmed: 23333712
Mol Oncol. 2018 Nov;12(11):1895-1916
pubmed: 30009399
Biomed Res Int. 2020 Sep 02;2020:5208279
pubmed: 33062681
Biochemistry. 1991 Feb 12;30(6):1682-91
pubmed: 1847072
Biochem Biophys Res Commun. 2006 Apr 28;343(1):252-9
pubmed: 16540085
Thromb Res. 1992 Mar 15;65(6):709-19
pubmed: 1636163