Plk1 overexpression induces chromosomal instability and suppresses tumor development

Guillermo de Cárcer (), Sharavan Vishaan Venkateswaran, Lorena Salgueiro, Aicha El Bakkali, Kalman Somogyi, Konstantina Rowald, Pablo Montañés, Manuel Sanclemente, Beatriz Escobar, Alba Martino, Nicholas McGranahan, Marcos Malumbres () and Rocío Sotillo ()
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Guillermo de Cárcer: Spanish National Cancer Research Centre (CNIO)
Sharavan Vishaan Venkateswaran: German Cancer Research Center (DKFZ)
Lorena Salgueiro: German Cancer Research Center (DKFZ)
Aicha El Bakkali: Spanish National Cancer Research Centre (CNIO)
Kalman Somogyi: German Cancer Research Center (DKFZ)
Konstantina Rowald: German Cancer Research Center (DKFZ)
Pablo Montañés: Spanish National Cancer Research Centre (CNIO)
Manuel Sanclemente: Spanish National Cancer Research Centre (CNIO)
Beatriz Escobar: Spanish National Cancer Research Centre (CNIO)
Alba Martino: Spanish National Cancer Research Centre (CNIO)
Nicholas McGranahan: University College London Cancer Institute
Marcos Malumbres: Spanish National Cancer Research Centre (CNIO)
Rocío Sotillo: German Cancer Research Center (DKFZ)

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05429-5

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