RSPO4
Overview
RSPO4 (R-spondin 4) is a secreted Wnt pathway agonist that enhances Wnt signaling by binding to LGR receptors and inhibiting RNF43/ZNRF3-mediated degradation of Frizzled receptors. RSPO4 overexpression upregulates canonical Wnt/beta-catenin signaling, promoting cell proliferation and survival.
Alterations observed in the corpus
- RSPO4 is epigenetically upregulated after treatment-associated DNA hypomethylation in recurrent IDH-mutant astrocytoma; RSPO4 upregulation is a consequence of treatment-related epigenetic evolution (demethylation at recurrence), contributing to Wnt/beta-catenin pathway activation in these tumors PMID:38117484.
Cancer types (linked)
- IDH-mutant astrocytoma (DIFG / ASTR) — RSPO4 upregulated via DNA hypomethylation at recurrence, particularly in tumors that received standard treatment (temozolomide and/or radiotherapy); part of the treatment-associated epigenetic transition toward an IDH-wildtype-like aggressive phenotype PMID:38117484.
Co-occurrence and mutual exclusivity
- RSPO4 upregulation co-occurs with epigenetic activation of MYB and HOXD13 in treatment-exposed recurrent IDH-mutant gliomas; these represent a coordinated epigenetic reprogramming toward malignant progression PMID:38117484.
Therapeutic relevance
- RSPO4-driven Wnt pathway activation in recurrent IDH-mutant glioma represents a potential therapeutic target; Wnt pathway inhibitors or RSPO4-targeted approaches could theoretically reduce proliferation in recurrent disease, though no direct therapeutic data exist in this context PMID:38117484.
Open questions
- Whether RSPO4 upregulation is a cause or consequence of the aggressive epigenetic reprogramming in recurrent IDH-mutant glioma, and whether targeting RSPO4/Wnt signaling can delay progression, requires functional validation.
Sources
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