FZD8
Overview
FZD8 (Frizzled class receptor 8) is a Wnt co-receptor that transduces canonical Wnt/β-catenin signaling. In pheochromocytoma/paraganglioma (PCC/PGL), FZD8 is a target of miR-375, a microRNA whose underexpression in MAML3 fusion-positive tumors is proposed to contribute to Wnt pathway activation within the Wnt-altered molecular subtype.
Alterations observed in the corpus
- FZD8 is a Wnt-pathway member overexpressed in MAML3 fusion-positive PCC/PGL; miR-375 (a negative regulator of FZD8) is underexpressed in these tumors, suggesting a miRNA-mediated mechanism for Wnt pathway activation in the Wnt-altered subtype of PCC/PGL (n=173, TCGA PCPG study) PMID:28162975.
Cancer types (linked)
- PHC / PGNG — FZD8 overexpression (via miR-375 underexpression) contributes to the Wnt-pathway activation signature in the MAML3 fusion-positive Wnt-altered subtype PMID:28162975.
Co-occurrence and mutual exclusivity
- FZD8 overexpression co-occurs with MAML3 fusion positivity, elevated DVL3 and β-catenin, and Wnt/Hedgehog target gene overexpression in PCC/PGL PMID:28162975.
Therapeutic relevance
- The Wnt-altered PCC/PGL subtype (defined in part by FZD8 overexpression) may be responsive to downstream β-catenin antagonists or STAT3 inhibitors — therapeutic hypotheses, not tested in this study PMID:28162975.
Open questions
- Whether miR-375 underexpression directly drives FZD8 overexpression and Wnt signaling in PCC/PGL, or whether additional mechanisms contribute, requires experimental validation PMID:28162975.
Sources
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