SIX4 and colorectal cancer: In addition, SIX1 and SIX4 have been shown to upregulate PI3K/AKT signaling in osteosarcoma and colorectal cancer, respectively, possibly through the downregulation of PTEN to further suppress apoptosis (Li et al., 2017; Yu et al., 2018; Na et al., 2019; Ji et al., 2020).