Fig. 2.
Molecular links between proteins implicated in self-renewal of normal and cancer stem cells (polycomb proteins Bmi-1, histone modifying protein Suz12 and Wnt/beta-catenin signaling) and EMT-TFs (Zeb1, Twist, Snail). Blue arrows indicate repressive/inhibitory actions, red arrows an upregulation. In the absence of active Wnt/beta-catenin signaling, GSK-3-beta phosphorylates both Snail and beta-catenin, thereby targeting them for ubiquitination and destruction in the proteasome. Both Snail and Zeb1 repress the CDH1 gene whose product, E-Cadherin (indicated through dashed blue line) binds and inactivates beta-catenin, thereby preventing it to associated with TCF/LEF-TFs (dashed blue line) and activate Wnt target genes in the nucleus.