We confirmed that, specifically in MSI‐H CRC cells, CT45A1 expression drives RHO‐ROCK/MLCK‐MLC2 signaling to enhance cancer cell resistance to NK cell cytotoxicity and generates a protective CIC structure, with CT45A1‐expressing cells becoming outer cells shielding the inner cancer cells from targeted antibody therapy and potentially subsequent antitumor immunity. This evidence concerns the gene RHO and cancer.