Overexpression of CT45A1 increased cancer cell resistance to NK cell killing via the RHO‐ROCK/MLCK‐MLC2 signaling axis (Fig. 4C–L) and promoted outer cell fate in homotypic CIC structures (Fig. 4M,N) without affecting cancer cell motility in MSI‐H CRC cell lines (Fig. 2C,D). Here, CT45A1 is linked to colorectal carcinoma.