Finally, the regulation of FOXA2 expression by ASCL1 is a cancer cell-intrinsic mechanism; we have not assessed whether extrinsic signals from the tumor microenvironment could also impact this pathway or others, as has been shown to be the case for L1CAM, a key determinant of metastatic competency in lung, colorectal, and breast adenocarcinomas17,44. Here, ASCL1 is linked to cancer.