WNT11
Overview
WNT11 encodes a Wnt ligand involved in non-canonical and canonical Wnt signaling. In pheochromocytoma/paraganglioma (PCC/PGL), WNT11 is overexpressed in MAML3 fusion-positive tumors as part of a broader Wnt/Hedgehog pathway activation driven by DNA hypomethylation in the Wnt-altered molecular subtype.
Alterations observed in the corpus
- Overexpressed in MAML3 fusion-positive PCC/PGL tumors; its upregulation is associated with promoter hypomethylation in the Wnt-altered subtype — inversely correlated with mRNA expression of corresponding target genes (p < 4e-10) PMID:28162975
Cancer types (linked)
- PHC / PGNG: WNT11 overexpression characterizes the Wnt-altered molecular subtype (defined by MAML3 fusions and CSDE1 mutations), which is associated with poor aggressive-disease-free survival and metastatic disease PMID:28162975
Co-occurrence and mutual exclusivity
- Co-overexpressed with WNT4 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 in MAML3 fusion-positive tumors (including WNT11 overexpression) supports investigation of β-catenin antagonists (e.g., PRI-274) and STAT3 inhibitors (e.g., BB1608); these are hypothesis-generating only, not tested in the study PMID:28162975
Open questions
- Whether WNT11 overexpression is a direct consequence of MAML3 fusion-driven DNA hypomethylation or reflects co-occurring epigenetic changes has not been directly tested.
Sources
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