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dc.contributor.authorHermanova, I
dc.contributor.authorZúñiga-García, P
dc.contributor.authorCaro-Maldonado, A
dc.contributor.authorFernandez-Ruiz, S
dc.contributor.authorSalvador, F
dc.contributor.authorMartín-Martín, N
dc.contributor.authorZabala-Letona, A
dc.contributor.authorNuñez-Olle, M
dc.contributor.authorTorrano, V
dc.contributor.authorCamacho, L
dc.contributor.authorLizcano, JM
dc.contributor.authorTalamillo, A
dc.contributor.authorCarreira, S
dc.contributor.authorGurel, B
dc.contributor.authorCortazar, AR
dc.contributor.authorGuiu, M
dc.contributor.authorLópez, JI
dc.contributor.authorMartinez-Romero, A
dc.contributor.authorAstobiza, I
dc.contributor.authorValcarcel-Jimenez, L
dc.contributor.authorLorente, M
dc.contributor.authorArruabarrena-Aristorena, A
dc.contributor.authorVelasco, G
dc.contributor.authorGomez-Muñoz, A
dc.contributor.authorSuárez-Cabrera, C
dc.contributor.authorLodewijk, I
dc.contributor.authorFlores, JM
dc.contributor.authorSutherland, JD
dc.contributor.authorBarrio, R
dc.contributor.authorde Bono, JS
dc.contributor.authorParamio, JM
dc.contributor.authorTrka, J
dc.contributor.authorGraupera, M
dc.contributor.authorGomis, RR
dc.contributor.authorCarracedo, A
dc.date.accessioned2020-05-18T10:13:12Z
dc.date.issued2020-06
dc.identifier.citationThe Journal of experimental medicine, 2020, 217 (6)
dc.identifier.issn0022-1007
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3607
dc.identifier.eissn1540-9538
dc.identifier.doi10.1084/jem.20191787
dc.description.abstractGene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1K78I, was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination.
dc.formatPrint
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleGenetic manipulation of LKB1 elicits lethal metastatic prostate cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-02-06
rioxxterms.versionofrecord10.1084/jem.20191787
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2020-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe Journal of experimental medicine
pubs.issue6
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
pubs.publication-statusPublished
pubs.volume217
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorGurel, Boraen
dc.contributor.icrauthorCarreira, Suzanneen
dc.contributor.icrauthorDe Bono, Johannen


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