Destabilization of β-catenin and RAS by KYA1797K effectively suppressed the stemness of colorectal CSCs as confirmed by suppression of the CSC markers including LGR5, CD44, CD133, and CD166 with significant inhibition of Wnt/β-catenin and RAS pathways in various spheroid cultured CRC cell lines. The gene discussed is PROM1; the disease is colorectal carcinoma.