Although we can not formally rule out the contribution of other E3 ligase –mediated effects on the functions of RIOK1, we were able to show here that FBXO6 links the activated RIOK1 to the degradation machinery and FBXO6 activity affects the cancer-supportive role of RIOK1 in CRC and GC. Here, FBXO6 is linked to colorectal carcinoma.