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Prohibitin (<i>PHB</i>) is a tumour suppressor gene with several different molecular activities. PHB overexpression leads to G1/S-phase cell cycle arrest, and PHB represses the androgen receptor (AR) in prostate cancer cells. PHB interacts with and represses members of the E2F family in a manner that may also be AR-linked, therefore making the AR:PHB:E2F interaction axis highly complex. <i>PHB</i> siRNA increased the growth and metastatic potential of LNCaP mouse xenografts in vivo. Conversely, <i>PHB</i> ectopic cDNA overexpression affected several hundred genes in LNCaP cells. Furthermore, gene ontology analysis showed that in addition to cell cycle regulation, several members of the <i>WNT</i> family were significantly downregulated (<i>WNT7B</i>, <i>WNT9A</i> and <i>WNT10B</i>), as well as pathways for cell adhesion. Online GEO data studies showed <i>PHB</i> expression to be decreased in clinical cases of metastatic prostate cancer, and to be correlated with higher WNT expression in metastasis. <i>PHB</i> overexpression reduced prostate cancer cell migration and motility in wound-healing assays, reduced cell invasion through a Matrigel layer and reduced cellular attachment. In LNCaP cells, <i>WNT7B</i>, <i>WNT9A</i> and <i>WNT10B</i> expression were also upregulated by androgen treatment and downregulated by androgen antagonism, indicating a role for AR in the control of these <i>WNT</i> genes. However, these <i>WNTs</i> were strongly cell cycle regulated. <i>E2F1</i> cDNA ectopic expression and <i>PHB</i> siRNA (both cell cycle promoting effects) increased <i>WNT7B</i>, <i>WNT9A</i> and <i>WNT10B</i> expression, and these genes were also upregulated as cells were released from G1 to S phase synchronisation, indicating further cell cycle regulation. Therefore, the repressive effects of PHB may inhibit <i>AR</i>, <i>E2F</i> and <i>WNT</i> expression and its loss may increase metastatic potential in human prostate cancer.