Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6546
Título
Plk1 overexpression induces chromosomal instability and suppresses tumor development
Autor(es)
de Carcer Diez, Guillermo CNIO | Venkateswaran, Sharavan Vishaan | Salgueiro, Lorena | El Bakkali, Aicha | Somogyi, Kalman | Rowald, Konstantina | Montañés, Pablo | Sanclemente, Manuel CNIO | Escobar, Beatriz CNIC | de Martino, Alba CNIO | McGranahan, Nicholas | Malumbres Martinez, Marcos CNIO | Sotillo, Rocío
Fecha de publicación
2018-08-01
Cita
Nat Commun. 2018; 9(1): 3012.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Polo-like kinase 1 (Plk1) is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene and an attractive cancer target. However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 overexpression results in abnormal chromosome segregation and cytokinesis, generating polyploid cells with reduced proliferative potential. Mechanistically, these cytokinesis defects correlate with defective loading of Cep55 and ESCRT complexes to the abscission bridge, in a Plk1 kinase-dependent manner. In vivo, Plk1 overexpression prevents the development of Kras-induced and Her2-induced mammary gland tumors, in the presence of increased rates of chromosome instability. In patients, Plk1 overexpression correlates with improved survival in specific breast cancer subtypes. Therefore, despite the therapeutic benefits of inhibiting Plk1 due to its essential role in tumor cell cycles, Plk1 overexpression has tumor-suppressive properties by perturbing mitotic progression and cytokinesis.
Palabras clave
POLO-LIKE KINASE | BREAST-CANCER | THERAPEUTIC TARGETS | ANTICANCER THERAPY | MAMMALIAN-CELLS | ESCRT MACHINERY | SCREEN | ANEUPLOIDY | EXPRESSION | MICE
Versión en línea
DOI
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