Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis

Abstract

Summary Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of non-cancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…The further investigation should focus on the detection of targeting properties of these ligands for preclinical trials and explore new target sites on membrane of hepatoma cells. Apart from ligands mentioned earlier, there are ligands whose receptors were found to have increased expression on HCC cells or play a role in HCC development, such as adenosine A2b receptor, 264 gamma-aminobutyric acid A receptor theta subunit, 265 androgen receptor, 266 E prostanoid receptor, 267 mitogenic insulin receptor A, 268 receptor of insulin-like growth factor 2, 269 and so on. On the other hand, the spatial properties of ligands can affect the targeting performance.…”

The miR-367-3p Increases Sorafenib Chemotherapy Efficacy to Suppress Hepatocellular Carcinoma Metastasis through Altering the Androgen Receptor Signals

“…Androgen/AR signals play important roles in normal liver function and in the development of liver diseases including HCC (Ma et al, 2014). Previous studies revealed a male predominance in HCC, which suggested that androgen/AR signals may promote hepatocarcinogenesis (Yeh and Chen, 2010).…”

A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogenesis and associates with tumor recurrence and poor survival of patients

“…Concordant with the male predominance of HCC, the sex hormone receptor androgen receptor (AR) plays a dominant role in hepatocarcinogenesis [17]. Our prior work underpinned cell cycle-related kinase (CCRK, also known as cyclin-dependent kinase 20) as an oncogenic effector of AR in HCC [18,19].…”