Survival of head and neck cancer cells relies upon LZK Kinase-mediated stabilization of mutant p53

2.50
Hdl Handle:
http://hdl.handle.net/10541/620554
Title:
Survival of head and neck cancer cells relies upon LZK Kinase-mediated stabilization of mutant p53
Authors:
Edwards, Zoe C; Trotter, Eleanor W; Torres-Ayuso, Pedro; Chapman, Phil; Wood, H; Nyswaner, Katherine; Brognard, John
Abstract:
Head and neck squamous cell carcinoma (HNSCC) includes epithelial cancers of the oral and nasal cavity, larynx, and pharynx and accounts for ∼350,000 deaths per year worldwide. Smoking-related HNSCC is associated with few targetable mutations but is defined by frequent copy-number alteration, the most common of which is gain at 3q. Critical 3q target genes have not been conclusively determined for HNSCC. Here, we present data indicating that MAP3K13 (encoding LZK) is an amplified driver gene in HNSCC. Copy-number gain at 3q resulted in increased MAP3K13 mRNA in HNSCC tumor samples and cell lines. Silencing LZK reduced cell viability and proliferation of HNSCC cells with 3q gain but not control cell lines. Inducible silencing of LZK caused near-complete loss of colony-forming ability in cells harboring 3q gain. These results were validated in vivo by evidence that LZK silencing was sufficient to reduce tumor growth in a xenograft model of HNSCC. Our results establish LZK as critical for maintaining expression of mutant stabilized p53. Cancer Res; 1-12. ©2017 AACR.
Affiliation:
Signalling Networks in Cancer, Cancer Research UK Manchester Institute
Citation:
Survival of head and neck cancer cells relies upon LZK Kinase-mediated stabilization of mutant p53. 2017 Cancer Res.
Journal:
Cancer Research
Issue Date:
31-Jul-2017
URI:
http://hdl.handle.net/10541/620554
DOI:
10.1158/0008-5472.CAN-17-0267
PubMed ID:
28760853
Type:
Article
Language:
en
ISSN:
1538-7445
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorEdwards, Zoe Cen
dc.contributor.authorTrotter, Eleanor Wen
dc.contributor.authorTorres-Ayuso, Pedroen
dc.contributor.authorChapman, Philen
dc.contributor.authorWood, Hen
dc.contributor.authorNyswaner, Katherineen
dc.contributor.authorBrognard, Johnen
dc.date.accessioned2017-09-08T14:59:46Z-
dc.date.available2017-09-08T14:59:46Z-
dc.date.issued2017-07-31-
dc.identifier.citationSurvival of head and neck cancer cells relies upon LZK Kinase-mediated stabilization of mutant p53. 2017 Cancer Res.en
dc.identifier.issn1538-7445-
dc.identifier.pmid28760853-
dc.identifier.doi10.1158/0008-5472.CAN-17-0267-
dc.identifier.urihttp://hdl.handle.net/10541/620554-
dc.description.abstractHead and neck squamous cell carcinoma (HNSCC) includes epithelial cancers of the oral and nasal cavity, larynx, and pharynx and accounts for ∼350,000 deaths per year worldwide. Smoking-related HNSCC is associated with few targetable mutations but is defined by frequent copy-number alteration, the most common of which is gain at 3q. Critical 3q target genes have not been conclusively determined for HNSCC. Here, we present data indicating that MAP3K13 (encoding LZK) is an amplified driver gene in HNSCC. Copy-number gain at 3q resulted in increased MAP3K13 mRNA in HNSCC tumor samples and cell lines. Silencing LZK reduced cell viability and proliferation of HNSCC cells with 3q gain but not control cell lines. Inducible silencing of LZK caused near-complete loss of colony-forming ability in cells harboring 3q gain. These results were validated in vivo by evidence that LZK silencing was sufficient to reduce tumor growth in a xenograft model of HNSCC. Our results establish LZK as critical for maintaining expression of mutant stabilized p53. Cancer Res; 1-12. ©2017 AACR.en
dc.language.isoenen
dc.rightsArchived with thanks to Cancer researchen
dc.titleSurvival of head and neck cancer cells relies upon LZK Kinase-mediated stabilization of mutant p53en
dc.typeArticleen
dc.contributor.departmentSignalling Networks in Cancer, Cancer Research UK Manchester Instituteen
dc.identifier.journalCancer Researchen

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