MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.
Antineoplastic Agents
/ therapeutic use
Cell Line, Tumor
Datasets as Topic
Drug Delivery Systems
Drug Resistance, Neoplasm
/ genetics
Epithelial-Mesenchymal Transition
Erlotinib Hydrochloride
/ therapeutic use
Genomics
Humans
MAP Kinase Kinase 1
/ antagonists & inhibitors
Metabolic Networks and Pathways
Phenotype
Protein Kinase Inhibitors
/ therapeutic use
Proteomics
Squamous Cell Carcinoma of Head and Neck
/ drug therapy
Whole Genome Sequencing
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 12 2019
11 12 2019
Historique:
received:
09
07
2019
accepted:
11
11
2019
entrez:
13
12
2019
pubmed:
13
12
2019
medline:
11
11
2020
Statut:
epublish
Résumé
Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge. In this study, we employed an integrated multi-omics approach to delineate mechanisms associated with acquired resistance to erlotinib by carrying out whole exome sequencing, quantitative proteomic and phosphoproteomic profiling. We observed amplification of several genes including AXL kinase and transcription factor YAP1 resulting in protein overexpression. We also observed expression of constitutively active mutant MAP2K1 (p.K57E) in erlotinib resistant SCC-R cells. An integrated analysis of genomic, proteomic and phosphoproteomic data revealed alterations in MAPK pathway and its downstream targets in SCC-R cells. We demonstrate that erlotinib-resistant cells are sensitive to MAPK pathway inhibition. This study revealed multiple genetic, proteomic and phosphoproteomic alterations associated with erlotinib resistant SCC-R cells. Our data indicates that therapeutic targeting of MAPK pathway is an effective strategy for treating erlotinib-resistant HNSCC tumors.
Identifiants
pubmed: 31827134
doi: 10.1038/s41598-019-55208-5
pii: 10.1038/s41598-019-55208-5
pmc: PMC6906491
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
Erlotinib Hydrochloride
DA87705X9K
MAP Kinase Kinase 1
EC 2.7.12.2
MAP2K1 protein, human
EC 2.7.12.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18793Références
Cancer Res. 2014 Apr 15;74(8):2340-50
pubmed: 24576830
Cancer Lett. 2011 Jul 1;306(1):85-91
pubmed: 21411223
Carcinogenesis. 2012 May;33(5):956-61
pubmed: 22327936
Clin Cancer Res. 2009 Mar 1;15(5):1585-92
pubmed: 19190133
Mol Cancer Ther. 2008 Sep;7(9):2894-903
pubmed: 18790770
PLoS One. 2011;6(11):e27529
pubmed: 22096589
Blood. 2017 Jan 26;129(4):497-508
pubmed: 27756750
Oncologist. 2009 Sep;14(9):900-8
pubmed: 19726454
Nat Rev Cancer. 2004 Dec;4(12):937-47
pubmed: 15573115
Eur J Cancer. 2006 Jan;42(1):109-11
pubmed: 16324836
Target Oncol. 2015 Sep;10(3):393-404
pubmed: 25341405
Oncogene. 2005 Mar 17;24(12):2032-41
pubmed: 15688013
Cancer Treat Rev. 2017 Feb;53:61-69
pubmed: 28073102
Int J Clin Exp Pathol. 2013 Jul 15;6(8):1493-504
pubmed: 23923067
J Clin Oncol. 2006 Jun 10;24(17):2666-72
pubmed: 16763281
Nucleic Acids Res. 2013 Jan;41(Database issue):D1063-9
pubmed: 23203882
Clin Cancer Res. 2015 Apr 15;21(8):1935-43
pubmed: 25351745
Nucleic Acids Res. 2019 Jan 8;47(D1):D590-D595
pubmed: 30321428
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Cancer Discov. 2016 Feb;6(2):147-153
pubmed: 26644315
Cancer Genet Cytogenet. 2001 Oct 1;130(1):14-21
pubmed: 11672768
Anticancer Res. 2011 May;31(5):1703-11
pubmed: 21617229
Oncol Rep. 2008 Jan;19(1):65-71
pubmed: 18097577
Genes Chromosomes Cancer. 2010 Jun;49(6):569-75
pubmed: 20232484
Bioinformatics. 2016 Jun 1;32(11):1740-2
pubmed: 26819473
Methods Mol Biol. 2013;1007:359-77
pubmed: 23666735
Mol Biotechnol. 2011 May;48(1):87-95
pubmed: 20927658
Sci Rep. 2016 Oct 31;6:36132
pubmed: 27796319
Nat Med. 2015 Jul;21(7):795-801
pubmed: 26030179
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9
pubmed: 9012815
Nat Rev Cancer. 2011 Jan;11(1):9-22
pubmed: 21160525
Otolaryngol Head Neck Surg. 2012 Oct;147(4):726-32
pubmed: 22568942
Cancer Res. 2005 Oct 15;65(20):9455-62
pubmed: 16230409
Oncol Rep. 2012 May;27(5):1653-9
pubmed: 22367090
PLoS One. 2013 Jul 31;8(7):e68966
pubmed: 23935914
Oncotarget. 2010 May;1(1):22-33
pubmed: 20930946
Oncoscience. 2018 Feb 23;5(1-2):21-38
pubmed: 29556515
J Cancer. 2017 Jul 20;8(12):2263-2268
pubmed: 28819429
PLoS One. 2016 Mar 10;11(3):e0150567
pubmed: 26962872
J Clin Oncol. 2004 Jan 1;22(1):77-85
pubmed: 14701768
Front Biosci (Landmark Ed). 2011 Jan 01;16:849-64
pubmed: 21196207
Cell Signal. 2007 Jul;19(7):1488-96
pubmed: 17314031
Cancer Res. 1988 Feb 1;48(3):589-601
pubmed: 3335022
Transl Lung Cancer Res. 2015 Feb;4(1):67-81
pubmed: 25806347
Oral Oncol. 2009 Oct;45(10):e155-60
pubmed: 19586795
Cancer Res. 2008 Apr 1;68(7):2391-9
pubmed: 18381447
J Biol Chem. 2012 Sep 7;287(37):31393-405
pubmed: 22778267
Mol Cancer Ther. 2013 Nov;12(11):2541-58
pubmed: 24026012
Nat Genet. 2012 Jun 10;44(7):783-7
pubmed: 22683711
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Int J Mol Med. 2019 Jul;44(1):103-114
pubmed: 31115482
Cancer Res. 2008 Jul 15;68(14):5524-8
pubmed: 18632602
J Cell Commun Signal. 2018 Dec;12(4):709-721
pubmed: 29480433
Nat Genet. 2011 Dec 25;44(2):133-9
pubmed: 22197931
Nat Genet. 2012 Jul 01;44(8):852-60
pubmed: 22751098
BMC Cancer. 2006 Oct 03;6:235
pubmed: 17018150
Cancer Metastasis Rev. 2009 Dec;28(3-4):335-44
pubmed: 20012924
Nucleic Acids Res. 2009 Jan;37(1):1-13
pubmed: 19033363
Head Neck. 2014 Nov;36(11):1547-54
pubmed: 24123531
Mol Cell Proteomics. 2002 May;1(5):376-86
pubmed: 12118079
Nature. 2015 Jan 15;517(7534):391-5
pubmed: 25409143
J Biol Chem. 1998 Aug 28;273(35):22848-55
pubmed: 9712920
J Biol Chem. 2012 Oct 5;287(41):34091-100
pubmed: 22902619
PLoS One. 2014 Jan 23;9(1):e85409
pubmed: 24465552
Genome Res. 2017 Apr;27(4):613-625
pubmed: 28179366
Oncotarget. 2016 Aug 9;7(32):51922-51933
pubmed: 27409162
Oncotarget. 2014 May 15;5(9):2608-21
pubmed: 24810989
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Mol Cancer Ther. 2007 Feb;6(2):532-41
pubmed: 17308052
Int J Oncol. 2017 Jun;50(6):2049-2058
pubmed: 28440469
Head Neck Oncol. 2009 Mar 02;1:6
pubmed: 19284526
Cancer Discov. 2012 Oct;2(10):934-47
pubmed: 22961667
Clin Cancer Res. 2010 May 1;16(9):2489-95
pubmed: 20406834
Oncotarget. 2014 Jan 30;5(2):530-43
pubmed: 24504069