CAR Assays
Overview of Constitutive Androstane Receptor (CAR)
CARs are members of the nuclear receptor superfamily that are found in the small intestine, liver, and gallbladder. CARs are involved in coordinating cellular responses to multiple chemical stimuli by regulating the expression of their target genes. CAR has been considered a sensor for controlling the metabolism and detoxification of drugs, but evidence is accumulating on the role of CAR in controlling lipid and glucose metabolism in the liver.
Functions of the CAR
Studies have revealed that CAR is inextricably linked to the regulation of hormones and lipids, drug metabolism, cancer development, and liver steatosis. In addition, scientists discovered that CAR plays a crucial role in regulating energy metabolism, suggesting that CAR has therapeutic potential in the prevention and treatment of obesity and type 2 diabetes and its clinical complications.
Mechanisms of CAR
CAR exerts multiple functions by the Wnt/β-catenin and Hippo/YAP pathways. The synergistic activation of the two signaling pathways may contribute to CAR-mediated liver cancer development.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| CAR | NR1I3 |
|
|
|
Published Data
| Paper Title | Role of the constitutive androstane receptor (CAR) in human liver cancer |
| Journal | Biochimica et Biophysica Acta (BBA)-Reviews on Cancer |
| Published | 2021 |
| Abstract | CARs are almost exclusively expressed in the liver. CARs are involved in the regulation of many key signaling pathways, such as drug and energy signaling. In mouse models, activation of CARs is involved in tumorigenesis by mediating proliferative and apoptotic signaling. However, there is evidence for species differences between CAR activity in animal models and humans. The researchers found that the way CARs work in rodent liver tumorigenesis does not apply to humans. Therefore, it is necessary to explore the role of CAR in human diseases, especially cancer. In addition, studies have shown the hepatoprotective effect of CAR in the human liver, more specifically, it is closely related to driving differentiation and liver regeneration. |
| Result |
The oncogenic role of CAR in rodent liver cancer has been well documented. However, the role of CAR in human hepatocellular carcinoma remains unclear. Numerous epidemiological studies suggest that the mode of action of CAR activation-induced hepatocarcinogenesis in rodents is not applicable in humans. Therefore, it is necessary to further explore the role of CAR activation in human hepatocellular carcinoma, more specifically, in hepatic normal stem cells (LNSCs). Since CAR is almost expressed in the liver and is involved in a variety of other key signaling pathways, the researchers speculated that CAR might inhibit LCSC activity by inhibiting LCSC activity or hindering dedifferentiation of differentiated cells into LCSC as well as suppressing key markers of LCSC.
|
Fig.1. Human CAR activation and liver tumorigenesis. (Bae, 2021)
Reference
- Bae, S.D.W.; et al. Role of the constitutive androstane receptor (CAR) in human liver cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2021; 1875(2): 188516.
