Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer.
Animals
Cyclic GMP-Dependent Protein Kinases
/ metabolism
Disease Models, Animal
Disease Progression
Drug Resistance, Neoplasm
/ drug effects
Enzyme Inhibitors
/ therapeutic use
Etoposide
/ therapeutic use
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ drug therapy
Mice
Neoplastic Cells, Circulating
/ metabolism
Nitric Oxide
/ metabolism
Nitric Oxide Synthase Type II
/ antagonists & inhibitors
Receptors, Notch
/ metabolism
Signal Transduction
/ genetics
Small Cell Lung Carcinoma
/ drug therapy
Soluble Guanylyl Cyclase
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 11 2021
17 11 2021
Historique:
received:
10
12
2020
accepted:
19
10
2021
entrez:
18
11
2021
pubmed:
19
11
2021
medline:
16
12
2021
Statut:
epublish
Résumé
Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC.
Identifiants
pubmed: 34789728
doi: 10.1038/s41467-021-26823-6
pii: 10.1038/s41467-021-26823-6
pmc: PMC8599617
doi:
Substances chimiques
Enzyme Inhibitors
0
Receptors, Notch
0
Nitric Oxide
31C4KY9ESH
Etoposide
6PLQ3CP4P3
Nitric Oxide Synthase Type II
EC 1.14.13.39
Cyclic GMP-Dependent Protein Kinases
EC 2.7.11.12
Soluble Guanylyl Cyclase
EC 4.6.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6652Subventions
Organisme : Cancer Research UK
ID : A27412
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A25254
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A20465
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A25146
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
Références
Cancer Res. 2016 Oct 1;76(19):5798-5809
pubmed: 27496711
PLoS Pathog. 2017 Oct 13;13(10):e1006668
pubmed: 29028833
Oncotarget. 2016 Jul 5;7(27):42385-42392
pubmed: 27285753
J Card Surg. 2002 Jul-Aug;17(4):336-9
pubmed: 12546082
Bioinformatics. 2019 Jun 1;35(12):2084-2092
pubmed: 30395178
Nat Commun. 2018 Sep 17;9(1):3787
pubmed: 30224629
Nat Protoc. 2017 Apr;12(4):828-863
pubmed: 28333914
Chem Res Toxicol. 2013 Mar 18;26(3):379-87
pubmed: 23402364
BMC Bioinformatics. 2019 Sep 2;20(1):450
pubmed: 31477009
Lancet Oncol. 2016 Jul;17(7):883-895
pubmed: 27269741
Development. 2013 May;140(9):1892-902
pubmed: 23571214
Clin Cancer Res. 2018 Oct 15;24(20):5153-5164
pubmed: 29941481
Nature. 2019 Oct;574(7777):206-210
pubmed: 31514202
J Thorac Cardiovasc Surg. 2018 Aug;156(2):515-522.e1
pubmed: 29653750
Cell Rep. 2018 Mar 6;22(10):2541-2549
pubmed: 29514083
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
J Virol. 1998 Nov;72(11):8463-71
pubmed: 9765382
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell Rep. 2019 Mar 12;26(11):2942-2954.e5
pubmed: 30865885
Pharmaceuticals (Basel). 2013 Feb 07;6(2):269-86
pubmed: 24275951
Nat Biotechnol. 2020 Mar;38(3):276-278
pubmed: 32055031
Nat Cancer. 2020 Apr;1:423-436
pubmed: 33521652
Nat Rev Cancer. 2009 May;9(5):338-50
pubmed: 19377506
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Dis Model Mech. 2018 Aug 6;11(8):
pubmed: 30082427
Breast Cancer Res. 2015 Feb 22;17:25
pubmed: 25849745
Cell Res. 2002 Dec;12(5-6):311-20
pubmed: 12528889
Nat Rev Cancer. 2019 May;19(5):289-297
pubmed: 30926931
PLoS Comput Biol. 2016 Apr 21;12(4):e1004873
pubmed: 27100738
BMC Bioinformatics. 2009 May 27;10:161
pubmed: 19473525
Nat Med. 2014 Aug;20(8):897-903
pubmed: 24880617
Biochim Biophys Acta. 2016 Jul;1860(7):1519-27
pubmed: 27095671
Neurosignals. 2002 Jul-Aug;11(4):175-90
pubmed: 12393944
Nat Rev Cancer. 2017 Dec;17(12):725-737
pubmed: 29077690
J Cell Sci. 2013 Apr 1;126(Pt 7):1626-36
pubmed: 23418348
Nature. 2017 May 18;545(7654):360-364
pubmed: 28489825
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Cancer Cell. 2011 Feb 15;19(2):244-56
pubmed: 21316603
J Thorac Oncol. 2020 Dec;15(12):1836-1843
pubmed: 32721553
Cancer Cell. 2017 Feb 13;31(2):286-299
pubmed: 28196596
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Cancer Res. 2010 Apr;8(4):578-91
pubmed: 20371672
Genome Med. 2018 Mar 28;10(1):25
pubmed: 29592813
J Cell Biochem. 2012 Nov;113(11):3587-98
pubmed: 22740515
Nature. 2015 Aug 6;524(7563):47-53
pubmed: 26168399
Cancer Discov. 2018 May;8(5):600-615
pubmed: 29483136
Nat Rev Clin Oncol. 2017 Sep;14(9):549-561
pubmed: 28534531
Cancer Cell. 2020 Jul 13;38(1):60-78.e12
pubmed: 32473656
Nat Protoc. 2006;1(2):729-48
pubmed: 17406303
Clin Cancer Res. 2019 Aug 15;25(16):5107-5121
pubmed: 31164374
Pharmacol Rev. 2010 Sep;62(3):525-63
pubmed: 20716671
J Biol Chem. 1994 May 20;269(20):14509-17
pubmed: 8182057
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Mol Cancer Res. 2017 Aug;15(8):1012-1016
pubmed: 28442585
Dev Cell. 2011 Aug 16;21(2):288-300
pubmed: 21839921
Br J Pharmacol. 2019 Feb;176(3):436-450
pubmed: 30427531
RNA. 2003 Apr;9(4):493-501
pubmed: 12649500
Nucleic Acids Res. 2019 Jul 2;47(W1):W171-W174
pubmed: 31106371
Annu Rev Biochem. 2012;81:533-59
pubmed: 22404633
Nat Commun. 2016 Nov 09;7:13322
pubmed: 27827359
Eur J Cardiothorac Surg. 2002 Jun;21(6):1105-10
pubmed: 12048093
EMBO J. 2017 Nov 2;36(21):3232-3249
pubmed: 29030483
Nat Med. 2017 Jan;23(1):114-119
pubmed: 27869802
Br J Cancer. 2008 Jun 3;98(11):1803-9
pubmed: 18506185