DVL3
Overview
DVL3 (Dishevelled segment polarity protein 3) is a cytoplasmic signal transducer in the canonical and non-canonical Wnt signaling pathways. Elevated DVL3 protein levels in pheochromocytoma and paraganglioma (PCC/PGL) have been reported in association with MAML3 fusion-positive tumors, which define the Wnt-altered molecular subtype — the subtype with the poorest clinical outcome.
Alterations observed in the corpus
- Elevated DVL3 protein (by RPPA) detected in MAML3 fusion-positive pheochromocytoma/paraganglioma tumors (PHC/PGNG); elevated alongside β-catenin and GSK3 in the Wnt-altered subtype in the TCGA PCPG multi-platform study (n=173) PMID:28162975.
Cancer types (linked)
- PHC / PGNG — DVL3 protein overexpression marks the Wnt-altered mRNA subtype, which contains all MAML3 fusion-positive tumors and is associated with poor aggressive-disease-free and metastasis-free survival PMID:28162975.
Co-occurrence and mutual exclusivity
- DVL3 protein elevation co-occurs with elevated β-catenin and GSK3 and with MAML3 fusion positivity in PCC/PGL PMID:28162975.
Therapeutic relevance
- The Wnt-altered subtype (defined partly by DVL3 elevation) may be responsive to β-catenin antagonists (e.g., PRI-274) or STAT3 inhibitors (e.g., BB1608), as proposed by the authors — not yet tested PMID:28162975.
Open questions
- Whether DVL3 protein overexpression in MAML3 fusion-positive tumors is a direct transcriptional target of the fusion or a secondary consequence of Wnt pathway activation is not established PMID:28162975.
Sources
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