dc.contributor.author | Hermanova, I | |
dc.contributor.author | Zúñiga-García, P | |
dc.contributor.author | Caro-Maldonado, A | |
dc.contributor.author | Fernandez-Ruiz, S | |
dc.contributor.author | Salvador, F | |
dc.contributor.author | Martín-Martín, N | |
dc.contributor.author | Zabala-Letona, A | |
dc.contributor.author | Nuñez-Olle, M | |
dc.contributor.author | Torrano, V | |
dc.contributor.author | Camacho, L | |
dc.contributor.author | Lizcano, JM | |
dc.contributor.author | Talamillo, A | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Cortazar, AR | |
dc.contributor.author | Guiu, M | |
dc.contributor.author | López, JI | |
dc.contributor.author | Martinez-Romero, A | |
dc.contributor.author | Astobiza, I | |
dc.contributor.author | Valcarcel-Jimenez, L | |
dc.contributor.author | Lorente, M | |
dc.contributor.author | Arruabarrena-Aristorena, A | |
dc.contributor.author | Velasco, G | |
dc.contributor.author | Gomez-Muñoz, A | |
dc.contributor.author | Suárez-Cabrera, C | |
dc.contributor.author | Lodewijk, I | |
dc.contributor.author | Flores, JM | |
dc.contributor.author | Sutherland, JD | |
dc.contributor.author | Barrio, R | |
dc.contributor.author | de Bono, JS | |
dc.contributor.author | Paramio, JM | |
dc.contributor.author | Trka, J | |
dc.contributor.author | Graupera, M | |
dc.contributor.author | Gomis, RR | |
dc.contributor.author | Carracedo, A | |
dc.date.accessioned | 2020-05-18T10:13:12Z | |
dc.date.issued | 2020-06-01 | |
dc.identifier.citation | The Journal of experimental medicine, 2020, 217 (6) | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3607 | |
dc.identifier.eissn | 1540-9538 | |
dc.identifier.doi | 10.1084/jem.20191787 | |
dc.description.abstract | Gene 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.format | Print | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ROCKEFELLER UNIV PRESS | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.title | Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-02-06 | |
rioxxterms.versionofrecord | 10.1084/jem.20191787 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2020-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The Journal of experimental medicine | |
pubs.issue | 6 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 217 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | De Bono, Johann | |