WNT4
Overview
WNT4 encodes a secreted Wnt ligand that participates in canonical and non-canonical Wnt signaling pathways. In pheochromocytoma/paraganglioma (PCC/PGL), WNT4 is overexpressed in MAML3 fusion-positive tumors as part of the Wnt/Hedgehog activation signature of the Wnt-altered molecular subtype.
Alterations observed in the corpus
- Overexpressed in MAML3 fusion-positive PCC/PGL tumors as part of the Wnt-altered subtype signature; upregulation is linked to promoter hypomethylation driven by aberrant MAML3 expression — inversely correlated with mRNA expression of target genes (p < 4e-10) PMID:28162975
Cancer types (linked)
- PHC / PGNG: WNT4 overexpression characterizes the Wnt-altered molecular subtype (defined by MAML3 fusions and CSDE1 mutations), associated with metastatic disease and poor aggressive-disease-free survival PMID:28162975
Co-occurrence and mutual exclusivity
- Co-overexpressed with WNT11 and WNT5A in MAML3 fusion-positive tumors; all three Wnt ligands are upregulated together as part of the Wnt-altered subtype signature PMID:28162975
Therapeutic relevance
- Wnt pathway activation (including WNT4 overexpression) in MAML3 fusion-positive PCC/PGL supports investigation of β-catenin antagonists (e.g., PRI-274) and STAT3 inhibitors (e.g., BB1608); hypothesis-generating, not tested in this study PMID:28162975
Open questions
- Whether individual Wnt ligand overexpression (WNT4, WNT11, WNT5A) is sufficient or whether combined activation is required for the Wnt-altered phenotype in PCC/PGL has not been resolved.
Sources
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