Of note, dysregulated expression of putative Nrf1-target genes (e.g., PTEN, CHD1, p53, MMP9, SMAD4, TCF4, and Wnt11) is implicated in Nrf1-deficient liver cancer development and malignant behavior, albeit the detailed mechanisms are required to be further determined in the future. This evidence concerns the gene SMAD4 and liver cancer.