Transcriptional repression of TWIST1 gene by Prospero-related homeobox 1 inhibits invasiveness of hepatocellular carcinoma cells.

Prospero-related homeobox 1 (PROX1) is important for liver development and down-regulation of this transcription factor in hepatocellular carcinoma (HCC) is associated with poor prognosis. We find that PROX1 expression is inversely correlated with the expression of epithelial-mesenchymal regulator TWIST1 in HCC cell lines and tumor tissues. We demonstrate that PROX1 directly binds to proximal promoter of TWIST1 gene to repress its transcription and inhibits its downstream target gene AKT2 expression which leads to reduction of cell migration and invasion. Moreover, PROX1 attenuates lung metastasis of HCC in vivo. These results support an anti-metastatic role of PROX1 via inhibiting TWIST1.