Oncogenic driver genes and tumor microenvironment determine the type of liver cancer

作者：Gang Wang, Qian Wang, Ning Liang, Hongyuan Xue, Tao Yang, Xuguang Chen, Zhaoyan Qiu, Chao Zeng, Tao Sun, Weitang Yuan, Chaoxu Liu, Zhangqian Chen, Xianli He · 发表于：Cell Death and Disease · 年份：2020 · DOI：10.1038/s41419-020-2509-x · 被引用次数：116 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Liver physiology and pathology、MicroRNA in disease regulation

Abstract Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor microenvironment, such as inflammatory microenvironments caused by viral hepatitis, alcoholic or nonalcoholic steatohepatitis, carbon tetrachloride (CCl 4 ), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and necroptosis-associated hepatic cytokine microenvironment caused by necroptosis of hepatocytes. However, the impact of different types of microenvironments on the phenotypes of PLC generated by distinct oncogenes is still unclear. In addition, the cell origin of different liver cancers have not been clarified, as far as we know. Recent researches show that mature hepatocytes retain phenotypic plasticity to differentiate into cholangiocytes. More importantly, our results initially demonstrated that HCC, ICC, and cHCC-ICC could originate from mature hepatocytes rather than liver progenitor cells (LPCs), hepatic stellate cells (HSCs) and cholangiocytes in AKT-driven, AKT/NICD-driven and AKT/CAT-driven mouse PLC models respectively by using hydrodynamic transfection methodology. Therefore, liver tumors originated from mature hepatocytes embody a wide spectrum of phenotypes from HCC to CC, possibly including cHCC-ICC and HB. However, the underlying mechanis...