At the pathway level, BMP4 promoted DNA replication and cell cycle progression through SMAD4-independent signalling (Fig. 5d), whereas this effect of BMP4 was not observed in SMAD4-expressing tumors (Fig. 5e). These findings are consistent with a previous report where cell cycle progression of hepatocellular carcinoma cells was accelerated by BMP4 treatment independent of SMAD4, potentially via the induction of CDK1 and cyclin B1 [69]. Here, SMAD4 is linked to hepatocellular carcinoma.