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dc.contributor.authorFrancis, JC
dc.contributor.authorGardiner, JR
dc.contributor.authorRenaud, Y
dc.contributor.authorChauhan, R
dc.contributor.authorWeinstein, Y
dc.contributor.authorGomez-Sanchez, C
dc.contributor.authorLefrançois-Martinez, A-M
dc.contributor.authorBertherat, J
dc.contributor.authorVal, P
dc.contributor.authorSwain, A
dc.date.accessioned2021-01-28T15:37:58Z
dc.date.available2021-01-28T15:37:58Z
dc.date.issued2021-02-16
dc.identifier.citationBritish journal of cancer, 2020
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4328
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-020-01166-z
dc.description.abstractBACKGROUND: Understanding the pathways that drive adrenocortical carcinoma (ACC) is essential to the development of more effective therapies. This study investigates the role of the transcription factor HOXB9 and other HOX factors in ACC and its treatment. METHODS: We used transgenic mouse models to determine the role of Hoxb9 in adrenal tumour development. Patient transcriptomic data was analysed for the expression of HOX genes and their association with disease. Drug response studies on various adrenocortical models were done to establish novel therapeutic options. RESULTS: Our human ACC dataset analyses showed high expression of HOXB9, and other HOX factors, are associated with poorer prognosis. Transgenic overexpression of Hoxb9 in the adrenal cortex of mice with activated Ctnnb1 led to larger adrenal tumours. This phenotype was preferentially observed in male mice and was characterised by more proliferating cells and an increase in the expression of cell cycle genes, including Ccne1. Adrenal tumour cells were found to be dependent on HOX function for survival and were sensitive to a specific peptide inhibitor. CONCLUSIONS: These studies show Hoxb9 can promote adrenal tumour progression in a sex-dependent manner and have identified HOX factors as potential drug targets, leading to novel therapeutic approaches in ACC.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.
dc.typeJournal Article
dcterms.dateAccepted2020-10-29
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41416-020-01166-z
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-11-20
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Development & Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Development & Cancer
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Development & Cancer
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Development & Cancer
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamDevelopment & Cancer
icr.researchteamDevelopment & Cancer
dc.contributor.icrauthorSwain, Amanda


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