RT Journal Article
T1 Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer
A1 Hermanova, Ivana
A1 Zuñiga-García, Patricia
A1 Caro-Maldonado, Alfredo
A1 Fernández Ruiz, Sonia
A1 Salvador, Fernando
A1 Martín-Martín, Natalia
A1 Zabala-Letona, Amaia
A1 Nuñez-Olle, Marc
A1 Torrano, Verónica
A1 Camacho, Laura
A1 Lizcano, José M.
A1 Talamillo, Ana
A1 Carreira, Suzanne
A1 Gure, Bora
A1 Cortazar, Ana R.
A1 Guiu, Marc
A1 López, José I.
A1 Martinez-Romero, Anabel
A1 Astobiza, Ianire
A1 Valcarcel-Jimenez, Lorea
A1 Lorente Pérez, María Del Mar
A1 Arruabarrena-Aristorena, Amaia
A1 Velasco Díez, Guillermo
A1 Gomez-Muñoz, Antonio
A1 Suarez-Cabrera, Cristian
A1 Lodewijk, Iris
A1 Flores Landeira, Juana María
A1 Sutherland, James D.
A1 Barrio, Rosa
A1 De Bono, Johann S.
A1 Paramio, Jesús M.
A1 Trka, Jan
A1 Graupera, Mariona
A1 Gomis, Roger R.
A1 Carracedo, Arkaitz
AB 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.
PB The Company of Biologists
SN 0022-0949, ESSN 1477-9145
YR 2020
FD 2020-03-27
LK https://hdl.handle.net/20.500.14352/6559
UL https://hdl.handle.net/20.500.14352/6559
LA eng
NO Unión Europea. Horizonte 2020
NO Unión Europea. FP7
NO Ministerio de Ciencia, Innovación y Universidades (MICIU)
NO Ministerio de Ciencia, Innovación y Universidades (MICIU)/Fondo Europeo de Desarrollo Regional (FEDER)
NO Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional(FEDER)
NO Gobierno Vasco.Basque Departamento de Salud
NO Gobierno Vasco. Departamento de Educación
NO Gobierno Vasco. Departamento de Industria, Comercio y Turismo
NO Fundación Vasca de Innovación e Investigación Sanitarias
NO Severo Ochoa Excellence Accreditation
NO Excellence Networks
NO European Training Networks Project
NO Fundación Cientíıfica Asociación Española Contra el Cancer
NO Fundación La Caixa
NO Fundació la Marató de TV3
NO Fundación BBVA
DS Docta Complutense
RD 9 may 2025