dc.contributor.author | Ruiz, EJ | |
dc.contributor.author | Pinto-Fernandez, A | |
dc.contributor.author | Turnbull, AP | |
dc.contributor.author | Lan, L | |
dc.contributor.author | Charlton, TM | |
dc.contributor.author | Scott, HC | |
dc.contributor.author | Damianou, A | |
dc.contributor.author | Vere, G | |
dc.contributor.author | Riising, EM | |
dc.contributor.author | Da Costa, C | |
dc.contributor.author | Krajewski, WW | |
dc.contributor.author | Guerin, D | |
dc.contributor.author | Kearns, JD | |
dc.contributor.author | Ioannidis, S | |
dc.contributor.author | Katz, M | |
dc.contributor.author | McKinnon, C | |
dc.contributor.author | O'Connell, J | |
dc.contributor.author | Moncaut, N | |
dc.contributor.author | Rosewell, I | |
dc.contributor.author | Nye, E | |
dc.contributor.author | Jones, N | |
dc.contributor.author | Heride, C | |
dc.contributor.author | Gersch, M | |
dc.contributor.author | Wu, M | |
dc.contributor.author | Dinsmore, CJ | |
dc.contributor.author | Hammonds, TR | |
dc.contributor.author | Kim, S | |
dc.contributor.author | Komander, D | |
dc.contributor.author | Urbe, S | |
dc.contributor.author | Clague, MJ | |
dc.contributor.author | Kessler, BM | |
dc.contributor.author | Behrens, A | |
dc.date.accessioned | 2022-01-07T10:18:25Z | |
dc.date.available | 2022-01-07T10:18:25Z | |
dc.date.issued | 2021-10-12 | |
dc.identifier.citation | eLife, 2021, 10 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4946 | |
dc.identifier.eissn | 2050-084X | |
dc.identifier.doi | 10.7554/elife.71596 | |
dc.description.abstract | Lung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient's 5-year survival rate is less than 5%. The ubiquitin-specific protease 28 (USP28) has been implicated in tumourigenesis through its stabilization of the oncoproteins c-MYC, c-JUN, and Δp63. Here, we show that genetic inactivation of Usp28-induced regression of established murine LSCC lung tumours. We developed a small molecule that inhibits USP28 activity in the low nanomole range. While displaying cross-reactivity against the closest homologue USP25, this inhibitor showed a high degree of selectivity over other deubiquitinases. USP28 inhibitor treatment resulted in a dramatic decrease in c-MYC, c-JUN, and Δp63 proteins levels and consequently induced substantial regression of autochthonous murine LSCC tumours and human LSCC xenografts, thereby phenocopying the effect observed by genetic deletion. Thus, USP28 may represent a promising therapeutic target for the treatment of squamous cell lung carcinoma. | |
dc.format | Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | eLIFE SCIENCES PUBL LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Neoplasms, Squamous Cell | |
dc.subject | Lung Neoplasms | |
dc.subject | Disease Models, Animal | |
dc.subject | Ubiquitin Thiolesterase | |
dc.subject | DNA-Binding Proteins | |
dc.subject | Transcription Factors | |
dc.subject | Gene Deletion | |
dc.title | USP28 deletion and small-molecule inhibition destabilizes c-MYC and elicits regression of squamous cell lung carcinoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-10-10 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.7554/elife.71596 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-10-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | eLife | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Behrens, Axel | |