The Wnt/β-catenin pathway is activated by miR-1246 in liver cancer stem cells

The Wnt/β-catenin signaling pathway drives stem cell proliferation and self-renewal (1). As the key transducer of the Wnt signal, the β-catenin transcriptional coactivator is tightly regulated (2). In the absence of Wnt, cytoplasmic β-catenin is found in a complex containing axis inhibition proteins 1 and 2 (AXIN1/2), adenomatous polyposis coli (APC), glycogen synthase kinase 3 beta (GSK3β), and casein kinase 1 epsilon (CK1ε). Here, it is phosphorylated on its amino terminal residues, ubiquitinated by beta-transducin repeat containing protein, and targeted for proteasomal degradation. When Wnt ligand is present, β-catenin levels are stabilized and it translocates into the nucleus to activate target gene expression.