Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.
Adrenergic beta-Antagonists
/ therapeutic use
Epithelial-Mesenchymal Transition
/ drug effects
Humans
Male
Prostate
/ metabolism
Receptors, Adrenergic, alpha-1
/ genetics
Receptors, Adrenergic, beta-1
/ genetics
Signal Transduction
/ drug effects
Tumor Microenvironment
/ genetics
Urinary Tract
/ metabolism
Urologic Diseases
/ genetics
Urologic Neoplasms
/ genetics
Adrenoceptors
Cell polarity
Fibrosis
Kidney disease
Phenotypic landscape
Urologic tumors
α- and β-adrenergic blockade
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
20 07 2021
20 07 2021
Historique:
received:
05
05
2021
accepted:
28
05
2021
entrez:
21
7
2021
pubmed:
22
7
2021
medline:
25
2
2022
Statut:
epublish
Résumé
The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract.
Identifiants
pubmed: 34284799
doi: 10.1186/s12964-021-00755-6
pii: 10.1186/s12964-021-00755-6
pmc: PMC8290582
doi:
Substances chimiques
ADRB1 protein, human
0
Adrenergic beta-Antagonists
0
Receptors, Adrenergic, alpha-1
0
Receptors, Adrenergic, beta-1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
78Subventions
Organisme : U.S. Department of Defense
ID : W81XWH-17-1-0590
Organisme : NCI NIH HHS
ID : R01 CA232574
Pays : United States
Organisme : National Institutes of Health/NCI
ID : R01CA232574
Organisme : NIDDK NIH HHS
ID : R01 DK116987
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148786
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120846
Pays : United States
Organisme : NINR NIH HHS
ID : R21 NR016518
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Am J Physiol Renal Physiol. 2012 Sep;303(5):F775-82
pubmed: 22674024
Kidney Int Suppl. 1996 Jun;55:S138-40
pubmed: 8743536
Am J Clin Exp Urol. 2019 Feb 18;7(1):46-60
pubmed: 30906804
Science. 2013 Jul 12;341(6142):1236361
pubmed: 23846904
Hum Pathol. 1992 Mar;23(3):211-22
pubmed: 1372877
Int J Mol Sci. 2017 Aug 02;18(8):
pubmed: 28767097
Br J Pharmacol. 1992 Dec;107(4):924-31
pubmed: 1361402
Br J Pharmacol. 1996 Jun;118(4):871-8
pubmed: 8799556
Anticancer Res. 2013 Nov;33(11):4695-700
pubmed: 24222103
Nephron. 1997;77(3):319-24
pubmed: 9375827
Oncogene. 2000 Aug 3;19(33):3811-5
pubmed: 10949937
Pharmacol Res. 2001 Sep;44(3):195-208
pubmed: 11529686
Nat Rev Cancer. 2020 Mar;20(3):143-157
pubmed: 31974491
Clin Nephrol. 2002 Dec;58(6):405-10
pubmed: 12508961
Eur Urol Focus. 2020 Sep 15;6(5):1086-1096
pubmed: 32540268
Kidney Int. 2015 Feb;87(2):350-8
pubmed: 25207878
Handb Exp Pharmacol. 2011;(202):283-306
pubmed: 21290232
Nature. 2019 May;569(7758):672-678
pubmed: 31092925
Prostate. 2015 Mar 1;75(4):440-7
pubmed: 25417911
Am J Clin Exp Urol. 2019 Jun 15;7(3):188-202
pubmed: 31317059
Int J Urol. 2008 Mar;15(3):193-9
pubmed: 18304211
N Engl J Med. 2016 Dec 8;375(23):2246-2254
pubmed: 27718781
Int Braz J Urol. 2014 Sep-Oct;40(5):683-9
pubmed: 25498280
JAMA Intern Med. 2019 Jun 1;179(6):812-819
pubmed: 31058923
Rev Urol. 2009 Fall;11(Suppl 1):S14-8
pubmed: 20126607
Nephron. 1980;25(2):77-81
pubmed: 7354883
Psychol Med. 1974 Nov;4(4):393-8
pubmed: 4456432
Onco Targets Ther. 2015 Apr 30;8:985-90
pubmed: 25995645
Cell. 2019 Apr 4;177(2):463-477.e15
pubmed: 30951672
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Pflugers Arch. 2003 Nov;447(2):205-13
pubmed: 12905035
Urology. 2005 May;65(5):1019-23
pubmed: 15882756
Asian J Androl. 2019 May-Jun;21(3):253-259
pubmed: 29848834
Am J Psychiatry. 1982 Jan;139(1):92-4
pubmed: 7055283
Development. 1999 Feb;126(5):1077-90
pubmed: 9927607
J Hypertens. 1996 Apr;14(4):489-94
pubmed: 8761899
PLoS One. 2013 Oct 23;8(10):e76922
pubmed: 24194850
Korean J Urol. 2010 Dec;51(12):811-8
pubmed: 21221199
J Am Soc Nephrol. 2013 Feb;24(2):229-42
pubmed: 23264683
J Auton Pharmacol. 1984 Sep;4(3):145-52
pubmed: 6092385
Respir Res. 2017 May 2;18(1):79
pubmed: 28464879
Br J Pharmacol. 2006 Feb;147 Suppl 2:S88-119
pubmed: 16465187
Nat Rev Cancer. 2017 Aug;17(8):457-474
pubmed: 28706266
Cancer Res. 2007 Dec 1;67(23):11344-52
pubmed: 18056461
Circulation. 2002 Nov 5;106(19):2491-6
pubmed: 12417548
J Urol. 2014 Apr;191(4):1003-8
pubmed: 24140548
Br J Pharmacol. 1995 Jul;115(5):781-6
pubmed: 8548177
J Pharmacol Sci. 2019 Mar;139(3):137-142
pubmed: 30665845
Eur J Pharmacol. 2009 Jan 28;603(1-3):73-8
pubmed: 19101535
Postgrad Med J. 1983;59 Suppl 3:161-3
pubmed: 6647201
Adv Chronic Kidney Dis. 2011 Jan;18(1):28-41
pubmed: 21224028
Nat Rev Nephrol. 2011 Oct 18;7(12):684-96
pubmed: 22009250
Curr Med Res Opin. 1991;12(8):516-20
pubmed: 1764955
Prostate. 1994 Aug;25(2):76-80
pubmed: 7518597
Br J Cancer. 2003 May 19;88(10):1615-21
pubmed: 12771931
Kidney Int. 2001 Feb;59(2):515-31
pubmed: 11168934
Cancer Res. 2006 Jan 1;66(1):464-72
pubmed: 16397262
Nat Rev Nephrol. 2015 May;11(5):264-76
pubmed: 25643664
J Hypertens. 2005 May;23(5):1077-82
pubmed: 15834295
Life Sci. 2000 May 19;66(26):2603-11
pubmed: 10883738
BMC Cancer. 2019 Nov 26;19(1):1142
pubmed: 31771535
J Hum Hypertens. 1996 Sep;10 Suppl 3:S59-64
pubmed: 8872829
Int J Mol Sci. 2016 Aug 16;17(8):
pubmed: 27537875
Cancer Prev Res (Phila). 2013 Sep;6(9):1000-6
pubmed: 23901046
Int J Nephrol Renovasc Dis. 2014 Feb 18;7:75-88
pubmed: 24600241
Naunyn Schmiedebergs Arch Pharmacol. 2008 Feb;376(6):397-406
pubmed: 18172615
J Am Soc Nephrol. 2009 May;20(5):933-9
pubmed: 18799718
Handb Exp Pharmacol. 2011;(202):307-18
pubmed: 21290233
Int J Epidemiol. 2013 Dec;42(6):1852-61
pubmed: 24536096
J Neurosurg. 2018 Oct 1;:1-9
pubmed: 30497198
J Pharmacol Exp Ther. 1996 Nov;279(2):948-55
pubmed: 8930204
J Clin Oncol. 2011 Jul 1;29(19):2635-44
pubmed: 21632503
Int J Impot Res. 2001 Dec;13(6):348-51
pubmed: 11918251
FASEB J. 2020 Nov;34(11):14892-14904
pubmed: 32939891
Electrolyte Blood Press. 2008 Jun;6(1):27-34
pubmed: 24459519
Adv Pharmacol. 1994;31:333-41
pubmed: 7532987
Nature. 2011 Jul 19;477(7366):549-55
pubmed: 21772288
Neurochem Int. 2007 Oct;51(5):328-31
pubmed: 17688972
Gene Ther Mol Biol. 2008;12(2):253-258
pubmed: 20717483
Bone Res. 2021 Feb 5;9(1):9
pubmed: 33547275
J Urol. 2007 Nov;178(5):2176-80
pubmed: 17870114
Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84
pubmed: 30459476
Kidney Int. 1980 Sep;18(3):309-22
pubmed: 7463946
Br J Urol. 1970 Apr;42(2):171-4
pubmed: 5420156
Hypertension. 2000 Dec;36(6):1083-8
pubmed: 11116129
J Cell Biol. 1994 Feb;124(4):619-26
pubmed: 8106557
J Clin Invest. 2013 Feb;123(2):874-86
pubmed: 23348742
Int Urol Nephrol. 2017 Mar;49(3):461-466
pubmed: 27822672
Urol Oncol. 2017 Jan;35(1):36.e1-36.e6
pubmed: 27687543
Biochim Biophys Acta. 1997 Oct 11;1358(3):215-20
pubmed: 9366252
Clin Exp Pharmacol Physiol. 1993 Jul-Aug;20(7-8):523-6
pubmed: 8104746
Cancer Biomark. 2011-2012;10(1):51-9
pubmed: 22297552
Biology (Basel). 2020 Feb 22;9(2):
pubmed: 32098331
J Pharmacol Exp Ther. 1994 Mar;268(3):1605-11
pubmed: 8138972
Front Oncol. 2015 Jan 12;4:375
pubmed: 25629002
J Urol. 1986 Jul;136(1):1-4
pubmed: 2423716
Postgrad Med J. 1976;52 Suppl 4:87-9
pubmed: 967773
Curr Cancer Drug Targets. 2004 Feb;4(1):85-95
pubmed: 14965270
Mol Cancer Res. 2012 Feb;10(2):197-207
pubmed: 22127496
Oncotarget. 2017 Jul 28;8(45):78507-78519
pubmed: 29108245
Breast Cancer (Auckl). 2020 Jun 17;14:1178223420931511
pubmed: 32595275
Neoplasia. 2007 Oct;9(10):830-9
pubmed: 17971903
Oncotarget. 2016 Oct 18;7(42):68314-68327
pubmed: 27582542
J Hypertens. 2001 May;19(5):907-11
pubmed: 11393674
Eur Urol. 2011 May;59(5):734-44
pubmed: 21269758
Pharmacology. 2012;90(5-6):242-6
pubmed: 23007551
Pharmacol Ther. 2000 Dec;88(3):281-309
pubmed: 11337028
Lab Invest. 2013 Mar;93(3):279-90
pubmed: 23318885
Basic Res Cardiol. 2000;95 Suppl 1:I41-5
pubmed: 11192352
Nat Med. 2006 Aug;12(8):939-44
pubmed: 16862152
Int J Mol Med. 2018 Jan;41(1):147-154
pubmed: 29138797
Lancet. 1981 Sep 12;2(8246):539-43
pubmed: 6115999
J Immunol. 1990 Sep 1;145(5):1430-4
pubmed: 2166759
Am J Nephrol. 2009;30(4):354-60
pubmed: 19609077
Oncogene. 2007 May 31;26(26):3777-88
pubmed: 17260025
Vasc Health Risk Manag. 2006;2(3):213-9
pubmed: 17326328
Kidney Int. 2012 Mar;81(5):442-8
pubmed: 22113526
Exp Nephrol. 1995 Sep-Oct;3(5):293-9
pubmed: 7583051
Br J Pharmacol. 2012 May;166(2):721-36
pubmed: 22122228
Eur J Pharmacol. 2016 Jun 15;781:36-44
pubmed: 27041645
Cancer Manag Res. 2012;4:431-45
pubmed: 23293538
Cochrane Database Syst Rev. 2002;(3):CD003781
pubmed: 12137711
Naunyn Schmiedebergs Arch Pharmacol. 2003 Aug;368(2):91-8
pubmed: 12861436
Br J Cancer. 2009 Sep 1;101(5):843-8
pubmed: 19654575
Acta Physiol (Oxf). 2006 Aug;187(4):433-46
pubmed: 16866775
Kidney Int. 2007 Jul;72(2):151-6
pubmed: 17495858
Kidney Int. 2006 Dec;70(11):1905-13
pubmed: 17021610
Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):412-6
pubmed: 9089674
Ecancermedicalscience. 2016 Oct 12;10:680
pubmed: 27899953
Handb Clin Neurol. 2015;130:61-108
pubmed: 26003239
Am J Cancer Res. 2015 Sep 15;5(10):2959-68
pubmed: 26693052
Mol Pharmacol. 2003 May;63(5):1104-16
pubmed: 12695539
Semin Immunol. 2014 Oct;26(5):357-68
pubmed: 24486056
BJU Int. 2019 Mar;123(3):511-518
pubmed: 30216624
Mol Pharmacol. 1994 Feb;45(2):171-5
pubmed: 8114668
Oncogenesis. 2020 Sep 24;9(9):84
pubmed: 32973139
Urology. 2014 Jan;83(1):56-61
pubmed: 24210570
Science. 2017 Oct 20;358(6361):321-326
pubmed: 29051371
Br J Urol. 1998 Mar;81 Suppl 1:48-50
pubmed: 9589017
Diabetes Spectr. 2015 Aug;28(3):175-80
pubmed: 26300610
Oncotarget. 2010 Nov;1(7):628-38
pubmed: 21317458
J Am Soc Nephrol. 1995 Nov;6(5):1482-90
pubmed: 8589327
Nature. 1996 Jan 4;379(6560):91-6
pubmed: 8538749
J Urol. 1998 Sep;160(3 Pt 1):937-43
pubmed: 9720591
Int J Mol Sci. 2020 Feb 28;21(5):
pubmed: 32121260
J Cancer Res Clin Oncol. 2019 Jul;145(7):1835-1843
pubmed: 31006846
Kardiologiia. 2020 Dec 15;60(11):1357
pubmed: 33487156
Int J Cancer. 2006 Jun 1;118(11):2744-9
pubmed: 16381019
J Urol. 2006 Jan;175(1):358-64
pubmed: 16406942
Cancer Res. 2002 Jan 15;62(2):597-602
pubmed: 11809715
J Physiol. 1972 Jun;223(3):633-47
pubmed: 5045736
Eur J Pharmacol. 2018 Nov 5;838:113-119
pubmed: 30201375
Neurourol Urodyn. 1994;13(3):315-21
pubmed: 7920688
Anticancer Res. 2016 Apr;36(4):1563-70
pubmed: 27069132
Biomed J. 2019 Jun;42(3):155-165
pubmed: 31466709
Am J Physiol Regul Integr Comp Physiol. 2019 Sep 1;317(3):R485-R490
pubmed: 31314543
J Biol Chem. 2003 Dec 19;278(51):51324-33
pubmed: 14551191
Nature. 2020 Feb;578(7795):449-454
pubmed: 32051587
Pharmacol Rev. 2001 Jun;53(2):319-56
pubmed: 11356987
Oncoscience. 2017 Aug 23;4(7-8):95-105
pubmed: 28966942
Eur Urol. 2011 Oct;60(4):691-8
pubmed: 21705134
Prostate Cancer Prostatic Dis. 2002;5(2):88-95
pubmed: 12496995
Urolithiasis. 2013 Oct;41(5):385-8
pubmed: 23877383
J Clin Med. 2020 Aug 25;9(9):
pubmed: 32854260
J Cell Sci. 2016 Dec 15;129(24):4563-4575
pubmed: 27875276
Onco Targets Ther. 2020 Oct 15;13:10535-10546
pubmed: 33116632
Cancer Res. 2000 Aug 15;60(16):4550-5
pubmed: 10969806
Eur J Cancer. 2021 Apr;147:106-116
pubmed: 33639323
Br J Pharmacol. 1992 Nov;107(3):803-7
pubmed: 1282075
J Clin Psychopharmacol. 1982 Feb;2(1):14-39
pubmed: 6121825
Hypertension. 1993 Jun;21(6 Pt 1):810-5
pubmed: 8500862
PLoS One. 2020 Nov 19;15(11):e0242429
pubmed: 33211759
Crit Rev Immunol. 2019;39(2):93-103
pubmed: 31679250
J Urol. 1993 Dec;150(6):2002-6
pubmed: 8230553
Int J Impot Res. 1997 Mar;9(1):17-26
pubmed: 9138055
Mol Biol Cell. 2008 Nov;19(11):4875-87
pubmed: 18799618
Prostate. 2016 Jun;76(8):757-66
pubmed: 26880388
Hypertens Res. 2001 Jul;24(4):359-63
pubmed: 11510747
BMB Rep. 2015 May;48(5):295-300
pubmed: 25748171
Kidney Res Clin Pract. 2019 Mar 31;38(1):6-14
pubmed: 30831675
Am J Hypertens. 2001 Jul;14(7 Pt 1):694-8
pubmed: 11465655
Pharmacy (Basel). 2018 May 14;6(2):
pubmed: 29757930
Basic Clin Pharmacol Toxicol. 2016 Jun;118(6):449-55
pubmed: 26617394
Rev Urol. 2006;8 Suppl 4:S35-42
pubmed: 17216000
JCI Insight. 2017 Sep 21;2(18):
pubmed: 28931758
Med Sci Monit. 2002 Sep;8(9):BR378-84
pubmed: 12221376
Nephrology (Carlton). 2019 May;24(5):497-503
pubmed: 30848004
J Urol. 1993 Aug;150(2 Pt 1):546-51
pubmed: 7686987
Cancer Causes Control. 2017 Apr;28(4):289-297
pubmed: 28224412
J Pharmacol Sci. 2010;112(2):151-7
pubmed: 20134112
Br J Pharmacol. 2011 May;163(2):438-46
pubmed: 21244368
Eur Urol. 2018 Sep;74(3):324-333
pubmed: 29699858
BMJ. 2013 Jun 18;346:f3406
pubmed: 23778271
Int J Cancer. 2011 May 15;128(10):2306-16
pubmed: 20715173
Kidney Int. 1997 Jul;52(1):171-81
pubmed: 9211360
J Urol. 1993 Mar;149(3):640-2
pubmed: 8094762
Kidney Int. 2001 Oct;60(4):1309-23
pubmed: 11576345
Anticancer Res. 2005 Nov-Dec;25(6B):4281-6
pubmed: 16309229
Consult Pharm. 2014 Dec;29(12):823-37
pubmed: 25521658
Anesth Prog. 2015 Spring;62(1):31-9
pubmed: 25849473
Biol Cell. 2004 Jun;96(5):343-8
pubmed: 15207902
J Clin Oncol. 2011 Jul 1;29(19):2645-52
pubmed: 21632501
Mol Med Rep. 2018 Apr;17(4):5213-5221
pubmed: 29393410
Am J Physiol Cell Physiol. 2002 May;282(5):C947-70
pubmed: 11940508
Clin Cancer Res. 2020 Apr 15;26(8):1803-1811
pubmed: 31754048
BJU Int. 2006 Apr;97(4):747-51, discussion 751
pubmed: 16536766
Circulation. 1987 Jan;75(1):204-12
pubmed: 2878741
Am J Cancer Res. 2020 Dec 01;10(12):4386-4398
pubmed: 33415006
J Urol. 1984 Sep;132(3):474-9
pubmed: 6206240
Am J Epidemiol. 2008 Feb 15;167(4):438-46
pubmed: 18048375
Br Med J. 1967 Apr 1;2(5543):50
pubmed: 6021004
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Cancer Sci. 2021 Jan;112(1):155-167
pubmed: 33007125
Cancer Cell. 2018 Jan 8;33(1):75-90.e7
pubmed: 29249692
J Biol Chem. 1998 Jun 12;273(24):14885-90
pubmed: 9614091
Cancer Sci. 2014 Jul;105(7):847-56
pubmed: 24815301
Andrologia. 1997 Mar-Apr;29(2):109-14
pubmed: 9111884
J Biol Chem. 1997 May 23;272(21):13937-44
pubmed: 9153256
Int J Mol Sci. 2020 Oct 26;21(21):
pubmed: 33114769
J Biol Chem. 2007 May 11;282(19):14094-100
pubmed: 17353197
Curr Opin Cell Biol. 2001 Oct;13(5):555-62
pubmed: 11544023
Cardiovasc Ther. 2020 Apr 29;2020:2478781
pubmed: 32426035
Psychoneuroendocrinology. 2007 Jun;32(5):470-9
pubmed: 17459596
Cochrane Database Syst Rev. 2014 Apr 02;(4):CD008509
pubmed: 24691989
Auton Neurosci. 2016 Oct;200:1-10
pubmed: 26278377
Brain Res Mol Brain Res. 1999 Jan 8;63(2):254-61
pubmed: 9878769
Circulation. 2003 Jun 3;107(21):2747-52
pubmed: 12742996
J Cell Biol. 2001 Nov 12;155(4):505-10
pubmed: 11696562
Br J Pharmacol. 2019 Jul;176(14):2358-2365
pubmed: 30719698
Int J Cancer. 2004 Nov 1;112(2):231-8
pubmed: 15352035
Urol Oncol. 2020 Oct;38(10):794.e11-794.e16
pubmed: 32307329
Oncol Rep. 2016 Jun;35(6):3135-42
pubmed: 27035124
Cancer Prev Res (Phila). 2019 Mar;12(3):185-194
pubmed: 30700439
J Cell Biochem. 2005 Feb 1;94(2):374-88
pubmed: 15526277
Neurourol Urodyn. 2005;24(2):142-8
pubmed: 15690361
Trends Pharmacol Sci. 2004 Sep;25(9):449-55
pubmed: 15559245
Cancer Res. 2010 Sep 15;70(18):7042-52
pubmed: 20823155
Mol Pharmacol. 1997 Dec;52(6):1071-80
pubmed: 9415717