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dc.contributor.authorErtay, A
dc.contributor.authorLiu, H
dc.contributor.authorLiu, D
dc.contributor.authorPeng, P
dc.contributor.authorHill, C
dc.contributor.authorXiong, H
dc.contributor.authorHancock, D
dc.contributor.authorYuan, X
dc.contributor.authorPrzewloka, MR
dc.contributor.authorColdwell, M
dc.contributor.authorHowell, M
dc.contributor.authorSkipp, P
dc.contributor.authorEwing, RM
dc.contributor.authorDownward, J
dc.contributor.authorWang, Y
dc.date.accessioned2021-01-28T15:37:53Z
dc.date.available2021-01-28T15:37:53Z
dc.date.issued2020-11-21
dc.identifier.citationCell death & disease, 2020, 11 (11), pp. 1001 - ?
dc.identifier.issn2041-4889
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4327
dc.identifier.eissn2041-4889
dc.identifier.eissn2041-4889en_US
dc.identifier.doi10.1038/s41419-020-03210-5
dc.identifier.doi10.1038/s41419-020-03210-5en_US
dc.description.abstractTriple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target therapeutically. Targeting synthetic lethality is an alternative approach for cancer treatment. TNBC shows frequent loss of phosphatase and tensin homologue (PTEN) expression, which is associated with poor prognosis and treatment response. To identify PTEN synthetic lethal interactions, TCGA analysis coupled with a whole-genome siRNA screen in isogenic PTEN-negative and -positive cells were performed. Among the candidate genes essential for the survival of PTEN-inactive TNBC cells, WDHD1 (WD repeat and high-mobility group box DNA-binding protein 1) expression was increased in the low vs. high PTEN TNBC samples. It was also the top hit in the siRNA screen and its knockdown significantly inhibited cell viability in PTEN-negative cells, which was further validated in 2D and 3D cultures. Mechanistically, WDHD1 is important to mediate a high demand of protein translation in PTEN-inactive TNBC. Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clinic-pathological information. Taken together, as an essential gene for the survival of PTEN-inactive TNBC cells, WDHD1 could be a potential biomarker or a therapeutic target for TNBC.
dc.formatElectronic
dc.format.extent1001 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleWDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-11-05
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41419-020-03210-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-11-21
rioxxterms.licenseref.startdate2020-11-21en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell death & disease
pubs.issue11
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/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
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/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.publication-statusPublished
pubs.volume11en_US
pubs.embargo.termsNot known
icr.researchteamLung Cancer Group
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorDownward, Julian David Harryen


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