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2020-06-01

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cc by-nc-sa (c) Hermanova et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171752

Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer

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https://doi.org/10.1084/jem.20191787

Resum

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 Lkbl 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, LKB1(K781), 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.

Matèries

Càncer de pròstata, Metàstasi

Matèries (anglès)

Prostate cancer, Metastasis

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

HERMANOVA, Ivana, ZÚÑIGA GARCÍA, Patricia, CARO MALDONADO, Alfredo, FERNANDEZ RUIZ, Sonia, SALVADOR, Fernando, MARTÍN MARTÍN, Natalia, ZABALA LETONA, Amaia, NUÑEZ OLLE, Marc, TORRANO, Verónica, CAMACHO, Laura, LIZCANO, José miguel, TALAMILLO, Ana, CARREIRA, Suzanne, GUREL, Bora, CORTAZAR, Ana rosa, GUIU, Marc, LÓPEZ, Jose i., MARTÍNEZ ROMERO, Anabel, ASTOBIZA, Ianire, VALCARCEL JIMENEZ, Lorea, LORENTE, Mar, ARRUABARRENA-ARISTORENA, Amaia, VELASCO, Guillermo, GOMEZ MUÑOZ, Antonio, SUAREZ CABRERA, Cristian, LODEWIJK, Iris, FLORES, Juana m., SUTHERLAND, James d., BARRIO, Rosa, BONO, Johann sebastian de, PARAMIO, Jesús m., TRKA, Jan, GRAUPERA I GARCIA-MILÀ, Mariona, GOMIS I CABRÉ, Roger, CARRACEDO, Arkaitz. Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer. _Journal of Experimental Medicine_. 2020. Vol. 217, núm. 6, pàgs. e20191787. [consulta: 15 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/171752]

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