Table 1 WNT ligands and signaling molecules associated with LC
Gene | Function | Mutation type/level of expression | References |
|---|---|---|---|
APC | Part of beta-catenin destruction complex | No mutation Suppressed expression by promoter methylation | [184] |
AXIN | Negative regulator of WNT signaling. Promotes beta-catenin phosphorylation which leads to beta-catenin degradation | No mutation Reduced expression | [185] |
CTNNB1 | Main component of canonical signaling, it serves as a transcription activator, binding to TCF/LEF family | Missense mutation of exon 3 results in substitution of Ser/Thr residues | [38] |
No mutation Increased expression in cytoplasm and nuclear compartment associated with poor prognosis | [186] | ||
DKK1 | Binding to LRP5/6 leads to its endocytosis and inhibition of canonical signaling | Increased expression detected in serum | [187] |
DKK3 | Secreted WNT antagonist | No mutation Reduced expression | [188] |
DVL1 | Required for FZD induced signaling pathway activation | No mutation Increased expression associated with advanced stages | [189] |
DVL2 | No mutation Increased expression is associated with advanced stages | [189] | |
DVL3 | No mutation Increased expression | [190] | |
FZD8 | Receptor for WNT proteins | No mutation Increased expression | [191] |
GSK-3-beta | Phosphorylates beta-catenin resulting in beta-catenin degradation | No mutation Ser9 phosphorylation is associated with poor prognosis | [192] |
SFRP1 | Inhibits WNT signaling by binding to WNT proteins | No mutation Reduced expression regulated by promoter hypermethylation | [193] |
TCF4 | Transcription factor that complexes with beta-catenin upon activated canonical WNT signaling | No mutation Increased expression in poorly differentiated tumor | [194] |
WIF1 | Binding to WNT proteins to prevent their interaction with receptors | No mutation Increased expression | [195] |
WNT1 | Non-canonical WNT ligand | No mutation Increased expression in NSCLC | [196] |
WNT11 | WNT ligand which can activate both canonical and non-canonical WNT pathway | No mutation Increased expression | [68] |
WNT2 | Canonical WNT ligand | No mutation Increased expression | [197] |
WNT3 | Canonical WNT ligand | No mutation Increased expression | [107] |
WNT5A | Non-canonical WNT ligand | No mutation Increased expression in SCC | [134] |
WNT7A | Non-canonical WNT ligand | No mutation Reduced expression due to promoter hypermethylation | [198] |
WNT7B | Canonical WNT ligand | No mutation Increased expression in AC | [199] |