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.
Oncotarget. 2016 Feb 23 [Epub ahead of print]
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, Albert A Geldof
Department of Urology, VU University Medical Center, Amsterdam, The Netherlands., Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands., Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands., Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands., Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands., Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands., Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands., Department of Urology, VU University Medical Center, Amsterdam, The Netherlands., Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands., Department of Urology, VU University Medical Center, Amsterdam, The Netherlands.