The decrease in the nuclear pool of SMURF2 would diminish its ability to negatively regulate the pro-tumorigenic factors residing in the nucleus (e.g., KLF5, YY1, ID1, SATB1 and others); while increased SMURF2 abundance in the cytoplasm would facilitate the cancer-promoting pathways, including EGFR-induced and KRAS-mediated signaling pathways and, suggestively, the WNT/β-CATENIN pathway (through the degradation of its negative regulators GSK-3β and AXIN) [9,16,17,18,20]. The gene discussed is AXIN1; the disease is cancer.