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.
Highlights
Prostate cancer (PCa) is the second most common cause of cancer related death in males in the Western countries [1]
CP110 expression maintained after transfection with either miR-129-3p mimic or inhibitor, with a modest modulation which is likely caused by endogenous CP110 expression
In the present study we show that when aggressive prostate cancer cells acquire metastatic capacity, a feedback loop is activated that controls centrosome number
Summary
Prostate cancer (PCa) is the second most common cause of cancer related death in males in the Western countries [1]. The progression of localized PCa to metastatic variants involves multiple sequential steps, including cell migration and invasive growth [2]. CA leads to promotion of tumor growth through induction of chromosomal missegregation and modulation of the microtubule cytoskeleton, causing enhanced directional migration and invasion of malignant cells [4,5,6]. CP110 is an evolutionary conserved centrosomal protein important for centrosome functioning [7,8,9], controlling cell migration [10]. CP110 overexpression caused CA and increased the invasive phenotype of cells [7, 11]. The actual contribution of CP110 in PCa metastasis has not been described
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