| First Author | Huang Q | Year | 2017 |
| Journal | Cancer Lett | Volume | 402 |
| Pages | 52-60 | PubMed ID | 28536011 |
| Mgi Jnum | J:243200 | Mgi Id | MGI:5907914 |
| Doi | 10.1016/j.canlet.2017.05.005 | Citation | Huang Q, et al. (2017) Tg737 regulates epithelial-mesenchymal transition and cancer stem cell properties via a negative feedback circuit between Snail and HNF4alpha during liver stem cell malignant transformation. Cancer Lett 402:52-60 |
| abstractText | Determining the origin of liver cancer stem cells is important for treating hepatocellular carcinoma. Tg737 deficiency plays an important role in the malignant transformation of liver stem cells, but the underlying mechanism remains unclear. Here we established a chemical-induced mouse hepatoma model and found that Tg737 and hepatocyte nuclear factor 4-alpha (HNF4alpha) expression decreased and epithelial-mesenchymal transition (EMT)-related marker expression increased during liver cancer development. To investigate the underlying mechanism, we knocked down Tg737 in WB-F344 (WB) rat hepatic oval cells. Loss of Tg737 resulted in nuclear beta-catenin accumulation and activation of the Wnt/beta-catenin pathway, which further promoted EMT and the malignant phenotype. XAV939, a beta-catenin inhibitor, attenuated WB cell malignant transformation due to Tg737 knockdown. To clarify the relationships of Tg737, the beta-catenin pathway, and HNF4alpha, we inhibited Snail and overexpressed HNF4alpha after Tg737 knockdown in WB cells and found that Snail and HNF4alpha comprise a negative feedback circuit. Taken together, the results showed that Tg737 regulates a Wnt/beta-catenin/Snail-HNF4alpha negative feedback circuit, thereby blocking EMT and the malignant transformation of liver stem cells to liver cancer stem cells. |
