From this result, we believe EGFL6 expression may associate with cancer cell self-renewal, and colony forming ability is related to the cell self-renewal ability [24] (Fig. 3a, b), we further explored the mechanism of EGFL6 in keeping the cell stemness by detecting the expression of several associated genes, including POU class 5 homeobox 1 (POU5F1), NANOG, and LIN28. The mRNA level of POU5F1, NANOG, and LIN28 all had obvious reductions when EGFL6 was knocked down in both HCT116 and HT29 (Fig. 4d, e). Here, POU5F1 is linked to cancer.