Storr Liver Centre, Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Westmead, NSW 2145, Australia.
Storr Liver Centre, Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Westmead, NSW 2145, Australia.
Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188516. doi: 10.1016/j.bbcan.2021.188516. Epub 2021 Jan 30.
The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily (subfamily 1, group I, member 3, also known as NR1I3) that is almost exclusively expressed in the liver. CAR interacts with key signalling pathways such as those involved in drug, energy and bilirubin metabolism. In mouse models, activation of CAR leads to tumorigenesis by inducing pro-proliferative and anti-apoptotic signalling. However, many previous reports have shown species differences between CAR activity in animal models and humans. Recent studies have demonstrated that the mode of action of CAR in rodent liver tumorigenesis is not applicable to humans. Despite this, many studies still continue to study the role of CAR in animal models, hence, there is a need to further explore the role of CAR in human diseases particularly cancers. While there is limited evidence for a role of CAR in human cancers, some studies have proposed a tumour-suppressive role of CAR in liver cancer. In addition, recent studies exploring CAR in human livers demonstrated a hepato-protective role for CAR in and more specifically, its ability to drive differentiation and liver regeneration. This review will discuss the role of CAR in liver cancer, with a focus on species differences and its emerging, tumour-suppressive role in liver cancer and its role in the regulation of liver cancer stem cells.
组成型雄烷受体 (CAR) 是核受体超家族的成员（亚家族 1，组 I，成员 3，也称为 NR1I3），几乎仅在肝脏中表达。CAR 与关键信号通路相互作用，如涉及药物、能量和胆红素代谢的信号通路。在小鼠模型中，CAR 的激活通过诱导促增殖和抗凋亡信号导致肿瘤发生。然而，许多先前的报告表明 CAR 在动物模型和人类中的活性存在物种差异。最近的研究表明，CAR 在啮齿动物肝脏肿瘤发生中的作用模式不适用于人类。尽管如此，许多研究仍在继续在动物模型中研究 CAR 的作用，因此，有必要进一步探索 CAR 在人类疾病特别是癌症中的作用。虽然 CAR 在人类癌症中的作用证据有限，但一些研究提出了 CAR 在肝癌中的肿瘤抑制作用。此外，最近研究 CAR 在人类肝脏中的作用表明 CAR 具有肝保护作用，更具体地说，其能够驱动分化和肝脏再生。这篇综述将讨论 CAR 在肝癌中的作用，重点讨论物种差异及其在肝癌中的新兴肿瘤抑制作用以及其在调节肝癌干细胞中的作用。
