HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations
Abstract 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...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-06-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202114133 |
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| author | Xiaoying Xu Beatrice Tassone Paola Ostano Atul Katarkar Tatiana Proust Jean‐Marc Joseph Chiara Riganti Giovanna Chiorino Zoltan Kutalik Karine Lefort Gian Paolo Dotto |
| author_facet | Xiaoying Xu Beatrice Tassone Paola Ostano Atul Katarkar Tatiana Proust Jean‐Marc Joseph Chiara Riganti Giovanna Chiorino Zoltan Kutalik Karine Lefort Gian Paolo Dotto |
| author_sort | Xiaoying Xu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-bbde4af1e1d84b45a602c7eeb0607f71 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-bbde4af1e1d84b45a602c7eeb0607f712025-08-20T03:46:24ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-06-0113712110.15252/emmm.202114133HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populationsXiaoying Xu0Beatrice Tassone1Paola Ostano2Atul Katarkar3Tatiana Proust4Jean‐Marc Joseph5Chiara Riganti6Giovanna Chiorino7Zoltan Kutalik8Karine Lefort9Gian Paolo Dotto10Department of Biochemistry, University of LausanneDepartment of Biochemistry, University of LausanneCancer Genomics Laboratory, Fondazione Edo ed Elvo TempiaDepartment of Biochemistry, University of LausanneDepartment of Biochemistry, University of LausanneDivision of Pediatric Surgery, Women‐Mother‐Child Department, Lausanne University Hospital (CHUV)Department of Oncology, University of TurinCancer Genomics Laboratory, Fondazione Edo ed Elvo TempiaUniversity Center for Primary Care and Public Health, University of LausanneDepartment of Biochemistry, University of LausanneDepartment of Biochemistry, University of LausanneAbstract 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.https://doi.org/10.15252/emmm.202114133genetic cancer susceptibilityHSD enzymesOXPHOSsquamous cell carcinomastem cell potential |
| spellingShingle | Xiaoying Xu Beatrice Tassone Paola Ostano Atul Katarkar Tatiana Proust Jean‐Marc Joseph Chiara Riganti Giovanna Chiorino Zoltan Kutalik Karine Lefort Gian Paolo Dotto HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations EMBO Molecular Medicine genetic cancer susceptibility HSD enzymes OXPHOS squamous cell carcinoma stem cell potential |
| title | HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations |
| title_full | HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations |
| title_fullStr | HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations |
| title_full_unstemmed | HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations |
| title_short | HSD17B7 gene in self‐renewal and oncogenicity of keratinocytes from Black versus White populations |
| title_sort | hsd17b7 gene in self renewal and oncogenicity of keratinocytes from black versus white populations |
| topic | genetic cancer susceptibility HSD enzymes OXPHOS squamous cell carcinoma stem cell potential |
| url | https://doi.org/10.15252/emmm.202114133 |
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