Institute of Developmental Biology and Regenerative Medicine, Southwest University, Beibei, Chongqing 400715, China.
Int J Mol Sci. 2022 Apr 24;23(9):4705. doi: 10.3390/ijms23094705.
Liver cancer is one of the most prevalent cancers in humans. Hepatocytes normally undergo dedifferentiation after the onset of hepatocellular carcinoma, which in turn facilitates the progression of cancer. Although the process of hepatocellular carcinoma dedifferentiation is of significant research and clinical value, the cellular and molecular mechanisms underlying it are still not fully characterized. We constructed a zebrafish liver cancer model based on overexpression of the oncogene to investigate the hepatocyte dedifferentiation in hepatocellular carcinoma. We found that, after hepatocarcinogenesis, hepatocytes dedifferentiated and the Notch signaling pathway was upregulated in this progress. Furthermore, we found that inhibition of the Notch signaling pathway or deficiency of both prevented hepatocyte dedifferentiation following hepatocellular carcinoma induction, reducing cancer metastasis and improving survival. In conclusion, we found that hepatocytes undergo dedifferentiation after hepatocarcinogenesis, a process that requires Notch signaling and likewise the activation of Sox9.
肝癌是人类最常见的癌症之一。肝癌发生后，肝细胞通常经历去分化，这反过来又促进了癌症的进展。尽管肝细胞癌去分化的过程具有重要的研究和临床价值，但它的细胞和分子机制仍未完全阐明。我们构建了一种基于过表达致癌基因 的斑马鱼肝癌模型，以研究肝癌中的肝细胞去分化。我们发现，在肝癌发生后，肝细胞发生去分化，Notch 信号通路在此过程中被上调。此外，我们发现抑制 Notch 信号通路或同时缺失 Notch 信号通路和 Sox9 均可阻止肝癌诱导后的肝细胞去分化，从而减少癌症转移并提高生存率。总之，我们发现肝癌发生后肝细胞发生去分化，这一过程需要 Notch 信号通路和 Sox9 的激活。
