Considering that PKCα has been shown to be both a physiological enhancer of β-catenin degradation [19] and a repressor of β-catenin co-transcriptional activity [18], our study put PKCα back in the spotlight by demonstrating key criteria of a relevant target to be stimulated for treating CRC: (i) PKCα integrity is preserved in most human CRCs and can thus be functionally activated; (ii) inducing PKCα function in the intestine epithelium is not deleterious; (iii) inducing PKCα function triggers the death of CRC cells; (iv) PKCα activity is drug-inducible. Here, PRKCA is linked to colorectal carcinoma.