Downregulation of PARVA promotes metastasis by modulating integrin-linked kinase activity and regulating MAPK/ERK and MLC2 signaling in prostate cancer.

backgroundMetastasis is the predominant cause of mortality in prostate cancer (PCa); however, the underlying mechanisms are largely uncharted. Here, we found that Parvin alpha (PARVA) is downregulated in PCa and its loss is associated with clinical metastasis. We further explored the mechanistic basis of this finding.

methodsThe mRNA expression of PARVA was identified by analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets. Immunohistochemistry (IHC) analysis was performed to evaluate the PARVA expression pattern in 198 PCa tissues, and 36 metastatic lymph node tissues. The function and molecular mechanism by which PARVA affects PCa were investigated

resultsThe microarray data analysis indicated that PARVA was drastically downregulated in primary and metastatic PCa compared with normal and primary samples, respectively (all P<0.001). Multivariate Cox regression analysis suggested that downregulation of PARVA in PCa was an independent prognostic factor for poor biochemical recurrence (BCR)-free survival (P<0.01). IHC analysis confirmed that PARVA was frequently downregulated in metastatic and primary PCa tissues (All P<0.001). Furthermore, PARVA expression was found to be associated with Gleason score, pathological stage, extracapsular extension, and lymph node invasion (All P<0.05). Knockdown of PARVA triggered cell migration and invasion

conclusionsOur study revealed that loss of PARVA expression in PCa promotes metastasis by releasing the inhibition of ILK activity, followed by the activation of MAPK/ERK and MLC2 signaling.