Notably, pharmacological degradation of TGFBR2 with the inhibitor ITD-1 potently abrogated metastatic outgrowth in both liver and lung colonization models.<h4>Conclusions</h4>Our findings delineate a novel KRAS-ERK-ZBTB20-TGFBR2 signaling axis that is a critical driver of metastasis colonization in KRAS-mutant CRC. Here, ZBTB20 is linked to colorectal carcinoma.