fig3

Figure 3. MUC1-C activates inflammatory pSTAT3 and NF-κB signaling in integrating EMT and stemness with DNA methylation. A. MUC1-C promotes STAT3 phosphorylation and forms a complex with pSTAT3 that induces expression of TWIST1, SNAIL, ALDH1, and CD44 (left). MUC1 also binds directly to NF-κB, promotes occupancy of NF-κB on the ZEB1 and DNMT1/3b promoters, and induces their expression (right). In turn, MUC1-C forms a complex with ZEB1 that recruits DNMTs, induces DNA methylation of the CDH1 CpG island, and suppresses CDH1 expression. B. MUC1-C interacts with TFs, such as pSTAT3 and, while not binding directly to DNA, forms complexes on target genes to promote their activation, as shown for TWIST1 (BioRender), as well as repression of others^[23,24].