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Constitutive androstane receptor (CAR) functions as a tumor suppressor via regulating stemness in liver cancer

  • 0Storr Liver Centre, Westmead Institute for Medical Research, Department of Medicine, the University of Sydney at Westmead Hospital, Westmead, NSW, 2145, Australia.
Scientific Reports +

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December 27, 2024

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December 27, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Constitutive androstane receptor (CAR) shows a tumor-suppressive role in human liver cancer, not oncogenic. Activating CAR reduces liver cancer stemness, proliferation, and invasion, suggesting new therapeutic potential.

Area Of Science

  • Hepatology
  • Cancer Biology
  • Molecular Pharmacology

Background

  • Constitutive androstane receptor (CAR) is a liver-expressed xenosensor.
  • Rodent studies suggest CAR has an oncogenic role in liver cancer, but its function in humans is unclear.
  • Investigating CAR's role in human liver cancer, particularly in liver cancer stem cells, is crucial.

Purpose Of The Study

  • To elucidate the functional roles of CAR in human liver cancer.
  • To examine the association between CAR and liver cancer stem cell markers.
  • To determine CAR's impact on liver cancer cell stemness and progression.

Main Methods

  • Bioinformatic analysis of CAR in human liver cancer and stem cell markers.
  • In vitro studies using siRNA and modulation of CAR activity.
  • Tumorsphere formation assays to assess cancer stem cell properties.

Main Results

  • Significant associations found between CAR and various signaling pathways, including stemness signaling.
  • CAR activation demonstrably reduced liver cancer cell stemness.
  • CAR activation repressed proliferation, migration, invasion, and tumorsphere formation (p < 0.05).

Conclusions

  • CAR plays a definitive tumor-suppressive role in human liver cancer.
  • CAR activation inhibits key cancer stem cell characteristics.
  • CAR activators may offer a novel therapeutic strategy for advanced hepatocellular carcinoma (HCC).

Keywords:

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