We believe that the chronic increase in plasma membrane cholesterol (20–230% change among orthogonal models) and rigidity observed in mutant APC cells and their GMPVs in the absence of stimulation with Wnt3a ligand, highlight the important role of constitutive activation of Wnt signaling in these CRC models when compared to “healthy” cells. The gene discussed is APC; the disease is colorectal carcinoma.