Epithelial-mesenchymal transition (EMT) is a critical process for tumor invasion and metastasis. Hypoxia may induce EMT, and upregulated β-catenin expression has been found in various tumors. In this study, we investigate the role of β-catenin in hypoxia-induced EMT in hepatocellular carcinoma (HCC). Induction of EMT in HCC cell lines by hypoxia was confirmed by altered morphology, expression change of EMT-associated markers and enhanced invasion capacity. We showed that hypoxia-induced EMT could be enhanced by addition of recombinant Wnt3a while it was repressed by β-catenin small interfering RNA. An interaction between β-catenin and hypoxia-induced factor-1α (hif-1α) was found, and an underlying competition for β-catenin between hif-1α and T-cell factor-4 was implied. Notably, increased hif-1α activity was accompanied with more significant EMT features. We also showed that the pro-EMT effect of β-catenin in hypoxia was deprived in the absence of hif-1α. Moreover, β-catenin was found to be responsible for the maintenance of viability and proliferation for tumor cells undergoing hypoxia. We further showed a correlation between hif-1α and β-catenin expression, and corresponding expression of EMT-associated markers in human HCC tissues. Our results suggest that Wnt/β-catenin signaling enhances hypoxia-induced EMT in HCC by increasing the EMT-associated activity of hif-1α and preventing tumor cell death.

Hepatocellular carcinoma (HCC) is one of the most common and therapeutically challenging malignancies worldwide. For patients ineligible for "curative resection" or liver transplantation, chemotherapy is an important minimally effective option. Strategies for chemosensitization are urgently needed. Here, we report that LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor, enhances the cytotoxicity of chemotherapy for HCC in vitro and in vivo. We found that LB

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Crops assemble and rely on rhizosphere-associated microbiomes for plant nutrition, which is crucial to their productivity. Historically, excessive nitrogen fertilization did not result in continuously increasing yields but rather caused environmental issues. A comprehensive understanding should be developed regarding the ways in which crops shape rhizosphere-associated microbiomes under conditions of increased nitrogen fertilization. In this study, we applied 16S and 18S ribosomal RNA gene profiling to characterize bacterial and fungal communities in bulk and rhizosphere soil of rice subjected to three levels of nitrogen fertilization for 5 years. Soil biochemical properties were characterized, and carbon-, nitrogen-, and phosphorus-related soil enzyme activities were investigated, by assays. Increasing nitrogen fertilization led to a decreasing trend in the variation of microbial community structures and demonstrated a more definite influence on fungal rather than bacterial community compositions and functions. Changes in the level of nitrogen fertilization significantly affected chemical properties such as soil pH, nutrient content, and microbial biomass levels in both rhizosphere and bulk soil. Soil enzyme activity levels varied substantially across nitrogen fertilization intensities and correlated more with the fungal than with the bacterial community. Our results indicated that increased nitrogen input drives alterations in the structures and functions of microbial communities, properties of soil carbon, nitrogen, and phosphorus, as well as enzyme activities. These results provide novel insights into the associations among increased nitrogen input, changes in biochemical properties, and shifts in microbial communities in the rhizosphere of agriculturally intensive ecosystems.