HSD17B7 gene in self-renewal and oncogenicity of keratinocytes from Black versus White populations.
HSD enzymes
OXPHOS
genetic cancer susceptibility
squamous cell carcinoma
stem cell potential
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 07 2021
07 07 2021
Historique:
revised:
19
05
2021
received:
15
02
2021
accepted:
20
05
2021
pubmed:
30
6
2021
medline:
26
10
2021
entrez:
29
6
2021
Statut:
ppublish
Résumé
Human populations of Black African ancestry have a relatively high risk of aggressive cancer types, including keratinocyte-derived squamous cell carcinomas (SCCs). We show that primary keratinocytes (HKCs) from Black African (Black) versus White Caucasian (White) individuals have on average higher oncogenic and self-renewal potential, which are inversely related to mitochondrial electron transfer chain activity and ATP and ROS production. HSD17B7 is the top-ranked differentially expressed gene in HKCs and Head/Neck SCCs from individuals of Black African versus Caucasian ancestries, with several ancestry-specific eQTLs linked to its expression. Mirroring the differences between Black and White HKCs, modulation of the gene, coding for an enzyme involved in sex steroid and cholesterol biosynthesis, determines HKC and SCC cell proliferation and oncogenicity as well as mitochondrial OXPHOS activity. Overall, the findings point to a targetable determinant of cancer susceptibility among different human populations, amenable to prevention and management of the disease.
Identifiants
pubmed: 34185380
doi: 10.15252/emmm.202114133
pmc: PMC8261506
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14133Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR039190
Pays : United States
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
Références
J Am Acad Dermatol. 2014 Apr;70(4):748-762
pubmed: 24485530
Cancer Med. 2016 Jun;5(6):1268-78
pubmed: 26990997
Mol Endocrinol. 2003 Sep;17(9):1715-25
pubmed: 12829805
Mol Cell Endocrinol. 2001 Jan 22;171(1-2):199-204
pubmed: 11165030
Br J Cancer. 2021 Jan;124(2):315-332
pubmed: 32901135
Mol Cell. 2020 Sep 17;79(6):1051-1065.e10
pubmed: 32877643
Am J Pathol. 2018 Feb;188(2):271-279
pubmed: 29137951
Cancer. 2019 Jun 15;125(12):2076-2088
pubmed: 30865299
J Endocrinol. 2012 Jan;212(1):27-40
pubmed: 22045753
Curr Opin Genet Dev. 2020 Jun;62:97-104
pubmed: 32745952
Cells. 2019 Jun 21;8(6):
pubmed: 31234354
Cancer Epidemiol Biomarkers Prev. 2013 Jun;22(6):1030-6
pubmed: 23576691
Genes Dev. 2007 Nov 1;21(21):2788-803
pubmed: 17974918
Nature. 2003 Feb 6;421(6923):639-43
pubmed: 12571598
Bioinformatics. 2012 Dec 15;28(24):3326-8
pubmed: 23060615
Anal Biochem. 2002 Dec 15;311(2):139-51
pubmed: 12470673
Cancer Cell. 2020 May 11;37(5):639-654.e6
pubmed: 32396860
Nat Rev Cancer. 2017 Jun;17(6):337-351
pubmed: 28450705
Bioinformatics. 2012 May 15;28(10):1353-8
pubmed: 22492648
Cell. 2007 Jan 26;128(2):325-39
pubmed: 17254970
Trends Cancer. 2017 Mar;3(3):181-197
pubmed: 28718431
Dev Cell. 2015 Nov 23;35(4):444-57
pubmed: 26609959
BMC Genomics. 2015 Dec 21;16:1093
pubmed: 26690364
PLoS One. 2015 Dec 11;10(12):e0144059
pubmed: 26658987
Virchows Arch. 2021 Apr;478(4):647-658
pubmed: 32812119
Science. 2019 Nov 15;366(6467):827-832
pubmed: 31727828
Oncotarget. 2017 May 2;8(18):30552-30562
pubmed: 28430630
J Glob Oncol. 2018 Sep;4:1-9
pubmed: 30241229
J Clin Invest. 2018 Jun 1;128(6):2581-2599
pubmed: 29757189
Cancer. 2020 Jan 15;126(2):381-389
pubmed: 31580491
Mol Endocrinol. 2011 May;25(5):754-66
pubmed: 21372145
Redox Biol. 2019 Jun;24:101214
pubmed: 31108462
Biochimie. 2020 Mar;170:106-117
pubmed: 31887335
Science. 2018 Dec 7;362(6419):1186-1189
pubmed: 30361388
Genes Dev. 2013 Mar 15;27(6):683-98
pubmed: 23512661
Semin Cancer Biol. 2017 Dec;47:125-146
pubmed: 28487205
Biochim Biophys Acta. 2009 Dec;1792(12):1113-21
pubmed: 19389473
Structure. 1996 Aug 15;4(8):905-15
pubmed: 8805577
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2302-6
pubmed: 2436229
Nat Med. 2006 Apr;12(4):446-51
pubmed: 16565722
Cancer Lett. 2018 Oct 1;433:33-42
pubmed: 29959055
Genome Med. 2020 May 29;12(1):51
pubmed: 32471518
Am Econ Rev. 2013 Feb;103(1):1-46
pubmed: 25506083
Nature. 2020 Oct;586(7831):741-748
pubmed: 33116287
BMC Bioinformatics. 2020 Jan 10;21(1):14
pubmed: 31924160
Nat Rev Cancer. 2006 Apr;6(4):270-80
pubmed: 16541145
Circulation. 2013 May 7;127(18):1888-902
pubmed: 23564668
Int Urol Nephrol. 2014 Oct;46(10):1941-6
pubmed: 24969031
JAMA Oncol. 2019 Jul 1;5(7):975-983
pubmed: 31120534
Cell. 2017 Sep 21;171(1):59-71.e21
pubmed: 28938123
Cell Metab. 2011 Oct 5;14(4):537-44
pubmed: 21982713
EMBO Mol Med. 2021 Jul 7;13(7):e14133
pubmed: 34185380
Methods Mol Biol. 2016;1420:255-85
pubmed: 27259745
Cancer Cell. 2016 May 9;29(5):622-637
pubmed: 27165741
Cell. 2005 Feb 25;120(4):483-95
pubmed: 15734681
Mol Oncol. 2020 Nov;14(11):2775-2786
pubmed: 32920960
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Genome Res. 2009 Sep;19(9):1655-64
pubmed: 19648217
Cell Metab. 2018 Jan 9;27(1):136-150.e5
pubmed: 29249690
Nature. 2009 Sep 24;461(7263):537-41
pubmed: 19727075
Diabetes. 2004 Mar;53(3):542-8
pubmed: 14988236
BMC Bioinformatics. 2008 Oct 10;9:428
pubmed: 18847484
Int J Cancer. 2017 Aug 15;141(4):731-743
pubmed: 28510291
Cold Spring Harb Perspect Med. 2013 Nov 01;3(11):
pubmed: 24186487
Int J Biochem Cell Biol. 2015 Aug;65:209-21
pubmed: 26073129
Sci Signal. 2013 Feb 05;6(261):ra8
pubmed: 23386745