PROX1 Promotes Hepatocellular Carcinoma Metastasis By Way of Up-Regulating Hypoxia-Inducible Factor 1α Expression and Protein Stability

• DOI: 10.1002/hep.26398
• Publication Date: 2013-03-16T09:34:38Z
• Authors: Yanfeng Liu; Ju-Bo Zhang; Yi Qin; Wei Wang; Lili Wei; Yigang Teng; Lei Guo; Bo Zhang; Zhenhai Lin; Jing Liu; Zheng-Gang Ren; Qing-Hai Ye; Youhua Xie
• Keywords: Surgical oncology; HDAC1

Hepatocellular carcinoma (HCC) is one of the most common cancers and third leading cause death from cancer worldwide. HCC has a very poor prognosis because tumor invasiveness, frequent intrahepatic spread, extrahepatic metastasis. The molecular mechanism invasiveness metastasis poorly understood. homeobox protein PROX1 required for hepatocyte migration during mouse embryonic liver development. In this study, we show that high expression in primary tissues associated with significantly worse survival early recurrence postoperative patients. Knockdown cells inhibited cell vitro nude mice while overexpression promoted these processes. PROX1's pro -metastasis activity likely attributed to its up-regulation hypoxia-inducible factor 1α ( HIF-1α ) transcription stabilization by recruiting histone deacetylase 1 (HDAC1) prevent acetylation HIF-1α, which subsequently induces an epithelial-mesenchymal transition response cells. We further demonstrated prognostic value using combination HDAC1 levels predict HCC. Conclusion : critical promotes (Hepatology 2013;58:692-705)