The close interaction between hypoxia-related proteins and metastasis in pancarcinomas.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 06 2022
30 06 2022
Historique:
received:
28
03
2022
accepted:
21
06
2022
entrez:
30
6
2022
pubmed:
1
7
2022
medline:
6
7
2022
Statut:
epublish
Résumé
Many primary-tumor subregions exhibit low levels of molecular oxygen and restricted access to nutrients due to poor vascularization in the tissue, phenomenon known as hypoxia. Hypoxic tumors are able to regulate the expression of certain genes and signaling molecules in the microenvironment that shift it towards a more aggressive phenotype. The transcriptional landscape of the tumor favors malignant transformation of neighboring cells and their migration to distant sites. Herein, we focused on identifying key proteins that participate in the signaling crossroads between hypoxic environment and metastasis progression that remain poorly defined. To shed light on these mechanisms, we performed an integrated multi-omics analysis encompassing genomic/transcriptomic alterations of hypoxia-related genes and Buffa hypoxia scores across 17 pancarcinomas taken from the PanCancer Atlas project from The Cancer Genome Atlas consortium, protein-protein interactome network, shortest paths from hypoxia-related proteins to metastatic and angiogenic phenotypes, and drugs involved in current clinical trials to treat the metastatic disease. As results, we identified 30 hypoxia-related proteins highly involved in metastasis and angiogenesis. This set of proteins, validated with the MSK-MET Project, could represent key targets for developing therapies. The upregulation of mRNA was the most prevalent alteration in all cancer types. The highest frequencies of genomic/transcriptomic alterations and hypoxia score belonged to tumor stage 4 and positive metastatic status in all pancarcinomas. The most significantly associated signaling pathways were HIF-1, PI3K-Akt, thyroid hormone, ErbB, FoxO, mTOR, insulin, MAPK, Ras, AMPK, and VEGF. The interactome network revealed high-confidence interactions among hypoxic and metastatic proteins. The analysis of shortest paths revealed several ways to spread metastasis and angiogenesis from hypoxic proteins. Lastly, we identified 23 drugs enrolled in clinical trials focused on metastatic disease treatment. Six of them were involved in advanced-stage clinical trials: aflibercept, bevacizumab, cetuximab, erlotinib, ipatasertib, and panitumumab.
Identifiants
pubmed: 35773405
doi: 10.1038/s41598-022-15246-y
pii: 10.1038/s41598-022-15246-y
pmc: PMC9246854
doi:
Substances chimiques
Hypoxia-Inducible Factor 1, alpha Subunit
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11100Informations de copyright
© 2022. The Author(s).
Références
Genes Dev. 2016 Apr 15;30(8):892-908
pubmed: 27083997
Curr Opin Genet Dev. 2016 Dec;41:8-13
pubmed: 27501156
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Nat Genet. 2019 Feb;51(2):308-318
pubmed: 30643250
Genome Biol. 2017 May 5;18(1):83
pubmed: 28476144
Cell Rep. 2018 Apr 3;23(1):227-238.e3
pubmed: 29617662
Nature. 1999 May 20;399(6733):271-5
pubmed: 10353251
Nat Rev Cancer. 2008 Mar;8(3):180-92
pubmed: 18273037
Biosystems. 2015 Jan;127:67-72
pubmed: 25451770
Trends Cancer. 2015 Sep;1(1):76-91
pubmed: 28741564
Br J Cancer. 2010 Jan 19;102(2):428-35
pubmed: 20087356
Front Pharmacol. 2021 Feb 26;12:598925
pubmed: 33716737
Cell. 2017 Feb 9;168(4):670-691
pubmed: 28187288
Genes Dev. 2004 Sep 15;18(18):2183-94
pubmed: 15371333
Sci Rep. 2021 Aug 26;11(1):17245
pubmed: 34446793
Int J Hematol. 2012 May;95(5):471-7
pubmed: 22562456
Proc Natl Acad Sci U S A. 1993 May 1;90(9):4304-8
pubmed: 8387214
Cell. 2018 Apr 5;173(2):371-385.e18
pubmed: 29625053
Cancer Res. 2019 Jun 15;79(12):3011-3027
pubmed: 31053634
Nat Rev Cancer. 2018 Nov;18(11):696-705
pubmed: 30293088
Nucleic Acids Res. 2016 Jan 4;44(D1):D548-54
pubmed: 26467481
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4
pubmed: 7539918
Cancer Res. 1999 Nov 15;59(22):5830-5
pubmed: 10582706
Science. 2016 Apr 8;352(6282):175-80
pubmed: 27124451
Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52
pubmed: 25352553
Genes (Basel). 2020 Jul 21;11(7):
pubmed: 32708340
J Clin Oncol. 2012 May 20;30(15):1777-83
pubmed: 22508814
J Proteome Res. 2019 Feb 1;18(2):623-632
pubmed: 30450911
Am J Blood Res. 2019 Feb 15;9(1):1-14
pubmed: 30899601
Sci Rep. 2018 Sep 18;8(1):13978
pubmed: 30228363
Front Mol Biosci. 2019 Aug 07;6:65
pubmed: 31440515
Cell Stem Cell. 2010 Aug 6;7(2):150-61
pubmed: 20682444
Nature. 2016 Jan 21;529(7586):298-306
pubmed: 26791720
J Biol Chem. 2017 Oct 13;292(41):16825-16832
pubmed: 28842498
Nat Cell Biol. 2000 Jul;2(7):423-7
pubmed: 10878807
Int J Mol Sci. 2017 May 23;18(6):
pubmed: 28545225
Sci Rep. 2020 May 22;10(1):8515
pubmed: 32444848
Biology (Basel). 2022 Jan 25;11(2):
pubmed: 35205052
Mol Cell Biol. 1998 Feb;18(2):732-41
pubmed: 9447969
Nat Med. 2017 Oct 6;23(10):1124-1134
pubmed: 28985214
Nat Rev Cancer. 2002 Jan;2(1):38-47
pubmed: 11902584
Nat Cancer. 2020 Jan;1(1):28-45
pubmed: 32656539
Nat Commun. 2017 Feb 16;8:14356
pubmed: 28205554
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198
pubmed: 31066453
J Neurosci Methods. 2010 Nov 30;193(2):217-25
pubmed: 20817029
Cancer Cell. 2018 Apr 9;33(4):721-735.e8
pubmed: 29622466
J Biol Chem. 1995 Jan 20;270(3):1230-7
pubmed: 7836384
Lancet. 2007 May 19;369(9574):1742-57
pubmed: 17512859
J Transl Med. 2019 Jan 9;17(1):14
pubmed: 30626396
Cell Rep. 2018 Apr 3;23(1):194-212.e6
pubmed: 29617660
Nat Rev Clin Oncol. 2011 May 31;8(7):393-404
pubmed: 21629216
Cancer Cell. 2016 Nov 14;30(5):694-707
pubmed: 27908735
Science. 2001 Apr 20;292(5516):464-8
pubmed: 11292862
Pharmacogenomics J. 2020 Feb;20(1):136-158
pubmed: 31616044
Semin Nucl Med. 2015 Mar;45(2):110-21
pubmed: 25704384
Nucleic Acids Res. 2016 Jan 4;44(D1):D481-7
pubmed: 26656494
Cell Rep. 2018 Apr 3;23(1):313-326.e5
pubmed: 29617669
Biochim Biophys Acta. 2016 Mar;1863(3):382-391
pubmed: 26079100
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Curr Opin Genet Dev. 2011 Feb;21(1):42-9
pubmed: 21145726
Nucleic Acids Res. 2018 Jan 4;46(D1):D950-D955
pubmed: 29088455
Nucleic Acids Res. 2019 Jan 8;47(D1):D1056-D1065
pubmed: 30462303
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Front Pharmacol. 2022 Jan 11;12:833000
pubmed: 35087412
Genome Integr. 2013 Oct 24;4(1):5
pubmed: 24152759
Annu Rev Med. 1998;49:407-24
pubmed: 9509272
Nat Clin Pract Oncol. 2008 Apr;5(4):206-19
pubmed: 18253104
Front Pharmacol. 2021 Apr 12;12:630658
pubmed: 33912047
Nat Rev Cancer. 2004 Jun;4(6):437-47
pubmed: 15170446
Cell. 2018 Apr 5;173(2):355-370.e14
pubmed: 29625052
Nucleic Acids Res. 2020 Jan 8;48(D1):D416-D421
pubmed: 31598703
Sci Rep. 2020 Mar 24;10(1):5285
pubmed: 32210335
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Med Res Rev. 2018 Jul;38(4):1404-1442
pubmed: 29278273
Nucleic Acids Res. 1999 Jan 1;27(1):29-34
pubmed: 9847135
Front Pharmacol. 2022 Mar 29;13:833174
pubmed: 35422702
Nat Metab. 2019 Apr;1(4):431-444
pubmed: 31984309
Cell. 2022 Feb 3;185(3):563-575.e11
pubmed: 35120664
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9433-8
pubmed: 12093899
Cancer Cell. 2018 Apr 9;33(4):690-705.e9
pubmed: 29622464
Nat Rev Cancer. 2011 Jun;11(6):393-410
pubmed: 21606941
Nat Med. 1995 Aug;1(8):822-6
pubmed: 7585187
Bioinformatics. 2018 Apr 1;34(7):1183-1191
pubmed: 29186335
Future Oncol. 2013 Nov;9(11):1623-36
pubmed: 24156323
Int J Hematol. 2012 May;95(5):464-70
pubmed: 22539362
Radiother Oncol. 1999 Nov;53(2):113-7
pubmed: 10665787
Cancer Res. 1998 Apr 1;58(7):1408-16
pubmed: 9537241
Nat Rev Cancer. 2020 Oct;20(10):555-572
pubmed: 32778778
Science. 1995 Sep 8;269(5229):1444-6
pubmed: 7660130
Curr Drug Metab. 2014 Feb;15(2):202-8
pubmed: 24524664
Cell. 2018 Apr 5;173(2):291-304.e6
pubmed: 29625048
Sci Rep. 2018 Nov 12;8(1):16679
pubmed: 30420728
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Cancer Discov. 2022 Jan;12(1):31-46
pubmed: 35022204
J Clin Oncol. 2010 Nov 20;28(33):4912-8
pubmed: 20956620
Biochim Biophys Acta Mol Basis Dis. 2019 Apr 1;1865(4):831-843
pubmed: 30266651
Acta Oncol. 2004;43(4):396-403
pubmed: 15303502
J Cell Physiol. 2010 Jan;222(1):17-22
pubmed: 19725055