Assessing the impact of epigenetic inhibitors on reversion of the chromatin landscape from metastatic to non-metastatic organoids

Colorectal cancer, a leading cause of cancer-related mortality due to distant metastases, is driven by activating mutations in the Wnt and MAPK pathways. Understanding the interplay between these crucial pathways during metastatic progression is essential for developing effective treatments. Here we developed an immunocompetent mouse model of metastatic colorectal cancer using in vivo orthotopic passaging. We demonstrate that highly metastatic tumor cells show increased accessibility of AP-1 TF motifs and less accessibility at TCF/LEF, suggesting higher MAPK and less WNT activity, respectively.