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FXR and liver carcinogenesis

Journal

ACTA PHARMACOLOGICA SINICA
Volume 36, Issue 1, Pages 37-43

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2014.117

Keywords

FXR; bile acid; liver cancer; nonalcoholic fatty liver disease; carcinogenesis; liver regeneration; inflammation

Funding

  1. National Natural Science Foundation of China [30972927]
  2. Foundation of Fujian Educational Committee [JA09111]
  3. NCI [1R01-CA139158]

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Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer.

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