The overexpression of AEG-1 increased the resistance of HCC cells to 5-FU, which is mediated by the induction of the transcription factor late SV40 Factor (LSF), resulting in an increase in the 5-FU substrate thymidylate synthase (TS) and increases in the drug-metabolizing enzyme dihydropyrimidine dehydrogenase (DPYD) [212]. Here, MTDH is linked to hepatocellular carcinoma.