In the present commentary, we discuss new observations stating that angiopoietin-like protein 1 (ANGPTL1) attenuates cancer metastasis and stemness through Forkhead box O-3a (Foxo3a)–SRY-related HMG-box-2 (Sox2) axis in colorectal cancer (Clin. This evidence concerns the gene ANGPTL1 and colorectal cancer.