While HES1 has been reported to induce EMT and promote metastasis and chemoresistance in CRC (Sun et al., 2017; van Es et al., 2005; Yuan et al., 2015), HES4 is identified by our present study capable of combating EMT induction in a BEST4-dependent manner that is regulated at both transcriptional and translational levels. Here, BEST4 is linked to colorectal carcinoma.