Collectively, these data indicate that combining NHERF1 inhibition in settings of β-catenin-silenced CRC cells, in which NHERF1 is highly/ectopically re-expressed, is mandatory to promote an autophagy-to-apoptosis switch in CRC cells refractory to single-β-catenin targeting. Here, NHERF1 is linked to colorectal carcinoma.