Murine xenograft models further demonstrated that silencing ECM1 within HCT15/FU cells enhanced their in vivo sensitivity to 5-FU, with corresponding reductions in N-cadherin, Bcl-2, p-AKT, p-PI3K, and p-GSK3β expression and increased Bax, caspase-3 levels, and E-cadherin, suggesting the ability of ECM1 to regulate the PI3K/AKT/GSK3β pathway to control CRC cell EMT induction and apoptotic resistance in vitro and in vivo. Here, BCL2 is linked to colorectal carcinoma.