2026-07-21T15:51:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65462024-11-29T17:58:15Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
de Carcer Diez, Guillermo
author
Venkateswaran, Sharavan Vishaan
author
Salgueiro, Lorena
author
El Bakkali, Aicha
author
Somogyi, Kalman
author
Rowald, Konstantina
author
Montañés, Pablo
author
Sanclemente, Manuel
author
Escobar, Beatriz
author
de Martino, Alba
author
McGranahan, Nicholas
author
Malumbres Martinez, Marcos
author
Sotillo, Rocío
funder
Fundación Ramón Areces
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Howard Hughes Medical Institute
funder
Asociación Española Contra el Cáncer
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Worldwide Cancer Research
2018-10-26T12:21:41Z
2018-10-26T12:21:41Z
2018-08-01
Nat Commun. 2018; 9(1): 3012.
10.1038/s41467-018-05429-5
2041-1723
2041-1723
Nature communications
30069007
http://hdl.handle.net/20.500.12105/6546
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.
eng
POLO-LIKE KINASE
BREAST-CANCER
THERAPEUTIC TARGETS
ANTICANCER THERAPY
MAMMALIAN-CELLS
ESCRT MACHINERY
SCREEN
ANEUPLOIDY
EXPRESSION
MICE
Plk1 overexpression induces chromosomal instability and suppresses tumor development
journal article
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