The enforced expression of SHP partially protected against liver cancer development in the FXR null mice [72]; hepatocyte-specific SHP overexpression showed a lower grade of dysplasia and reduced cell proliferation in the FXR KO mice, although the incidence or size of the liver tumor was not affected, suggesting the possibilities of FXR-dependent but SHP-independent hepatic tumorigenesis. This evidence concerns the gene NR1H4 and liver cancer.