Oncotarget

Research Papers:

miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110

Irene V. Bijnsdorp _, Jasmina Hodzic, Tonny Lagerweij, Bart Westerman, Oscar Krijgsman, Jurjen Broeke, Frederik Verweij, R. Jonas A. Nilsson, Lawrence Rozendaal, Victor W. van Beusechem, Jeroen A. van Moorselaar, Thomas Wurdinger and Albert A. Geldof

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Oncotarget. 2016; 7:16676-16687. https://doi.org/10.18632/oncotarget.7572

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Abstract

Irene V. Bijnsdorp1, Jasmina Hodzic2, Tonny Lagerweij3, Bart Westerman3, Oscar Krijgsman4,5, Jurjen Broeke6, Frederik Verweij4, R. Jonas A. Nilsson3,7, Lawrence Rozendaal4, Victor W. van Beusechem2, Jeroen A. van Moorselaar1, Thomas Wurdinger3,8,*, Albert A. Geldof1,*

1Department of Urology, VU University Medical Center, Amsterdam, The Netherlands

2Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

3Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands

4Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

5Department of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

6Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands

7Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

8Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

*These authors have contributed equally to this work

Correspondence to:

Irene V. Bijnsdorp, e-mail: iv.bijnsdorp@vumc.nl

Keywords: prostate cancer, centrosome, CP110, miR-129-3p, metastasis

Received: October 10, 2015    Accepted: February 02, 2016    Published: February 23, 2016

ABSTRACT

The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.


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