BTK and neoplasm: Since PI3K–AKT–mTOR signaling is one of the critical downstream pathways of CXCL8 and IL11 in mediating cancer metastasis and EMT15,16, to test whether PI3K–ATK–mTOR signaling pathway involved in CUL1 induced tumor metastasis, we knocked down CUL1 in MDA-MB-231 cells, and western blotting results showed that CUL1 knockdown significantly suppressed p-AKT, p-mTOR, and p-P70S6K protein levels (Fig. 8a).