These cells were subcutaneously injected into nude mice. All the mice in both groups developed tumors. After 8 weeks, five out of six mice in the control group were found to have lung metastases (mean of number of metastatic nodules per lung = 4.7 ± 3.3), while none in the MHCC-97H-si1646 group developed lung metastases (P = 0.015) (Fig. 7F). Although several genes associated with HCC metastasis have been identified in the past few years,[24, 26-31] the molecular mechanism of HCC invasiveness and metastasis is still not well understood. Much evidence

has been presented to indicate that EMT is crucial for cancer invasiveness and metastasis.[3, 4, 32] Nevertheless, Napabucasin a more in-depth understanding of the factors promoting EMT in HCC and HCC metastasis is urgently needed in order to identify specific biomarkers for improving HCC prognosis and treatment. Because of its essential function in promoting hepatocyte migration during mouse embryonic liver development, PROX1′s role in HCC invasiveness and metastasis is intriguing but unsolved. In this study, we demonstrated selleckchem that PROX1 promoted HCC cell migration and invasiveness in vitro and HCC metastasis to lymph nodes and lung in nude mice. The molecular mechanism underlying PROX1′s

Pro-metastasis activity is most likely attributed to its up-regulation of HIF-1α transcription and HIF-1α protein stability, which consequently induces an EMT response in HCC cells. Accordingly, high PROX1 expression in primary HCC tissues is associated with significantly worse postoperative survival and early tumor recurrence. Collectively, we pinpointed PROX1 for the first time as a critical

Tideglusib factor that promotes HCC metastasis. The role of PROX1 in HCC development was unsolved because previous reports had not investigated the role of PROX1 in HCC metastasis. Dudas et al.[19] analyzed PROX1 mRNA levels in small numbers of normal, cirrhotic, and HCC liver samples using quantitative RT-PCR and northern blot, but no clear correlation with disease was observed. In another earlier work, however, Shimoda et al.[18] also used quantitative RT-PCR to evaluate PROX1 mRNA levels in 52 HCC samples and identified a positive correlation between PROX1 mRNA level and better prognosis. The discrepancy between the latter results and our data reported in this work might be attributed to several factors. First, PROX1 mRNA expression rather than protein expression was examined in the previous report. High PROX1 mRNA expression itself does not necessarily result in high PROX1 protein expression. Second, the differences in HCC patients’ background, especially a history of infection with HCC-inducing pathogens, may have a profound influence on HCC development. For example, only one-fourth of the HCC patients in Shimoda et al.’s study had a history of HBV infection.