CREB1 and hepatocellular carcinoma: AKR1D1, an enzyme involved in BA metabolism, plays an important tumor suppressor role in hepatocellular carcinoma, and its deficiency significantly accelerated the progression of hepatocellular carcinoma by a mechanism that may be a significant increase in secondary BA iso-LCA impairs the cytotoxic function of CREB1 by inhibiting its phosphorylation in NK cells, dose-dependently decreasing the ability of NK cells to kill tumor cells [60].