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. 2022 Sep 16;66(4):319–331. doi: 10.1042/EBC20220016

Figure 1. Simplified overview of the WNT signaling network.

Figure 1

WNT signals are transmitted to the canonical and noncanonical signaling cascades. Canonical WNT signaling is transmitted through Frizzled and LRP5/6 receptors to the transcriptional outputs depending on the β-catenin-TCF/LEF complex to up-regulate the expression of target genes, such as ALDH1A1, ASCL2, ATF3, AXIN2, BAMBI, CCL28, CCND1, CD274 (PD-L1), CLDN1, CTLA4, DKK1, EOMES, FGF20, FZD7, IL10, LEF1 (Lef-1), LGR5, MYC, NKD1, NOTUM, OPN, PROX1, RNF43, SNAI1 (Snail), TCF7 (Tcf-1), TNFRSP19 (Troy), WISP1 and ZNRF3. Noncanonical WNT signaling is transmitted through Frizzled or ROR1/2 receptors to the Gq-PLC-IP3-Ca2+, Rac1-JNK and RhoA-ROCK signaling branches to regulate transcriptional outputs depending on the NFAT, AP-1 and YAP-TEAD complexes. WNT signaling cascades cross-talk with the TGFβ (transforming growth factor-β), FGF (fibroblast growth factor), Hedgehog, Notch and YAP signaling cascades in the tumor microenvironment and affect cancer stem cells, cancer-associated fibroblasts, endothelial cells and immune cells.