Figure 5

Wnt signaling schematic identifying well known mechanisms of interaction overlaid with gene expression regulation in TNBC tumors in the Quebec, Georgia, and MSKCC-99 cohorts and basal-like carcinomas in the UNCCH-186 and Stockholm-159 cohorts. Upregulated components include frizzled receptors, which when bound by Wnt ligands sequester disheveled (DVL1), breaking up a β-catenin phosphorylating complex composed of Axin, APC, and GSK-3β. This complex, when intact phosphorylates β- catenin on Serines 33, 37, and Threonine 41. Phosphorylated β-catenin can either become poly-ubiquitinated by the phosphate dependent ubiquitin ligase, BTRC, and subsequently degraded by the proteasome, or phosphorylated β-catenin can bind to P, N, and E type cadherins that enhance cytosolic β-catenin turnover. When the DVL, Axin, GSK-3β, and APC β-catenin phosporylating complex is not intact β-catenin does not become phosphorylated leading to transcriptional active β-catenin which can translocate to the nucleus and transcribes Wnt transcriptional target in combination with other co-activators including TCF7L2 (also known as TCF4), BCL9, and CREB binding protein (CBP).