WNT5A

Overview

WNT5A (Wnt family member 5A) encodes a secreted glycoprotein that activates non-canonical WNT signaling pathways involved in cell polarity, migration, and differentiation. In cancer genomics, WNT5A over-expression defines a transcriptional sub-group of extra-cranial malignant rhabdoid tumors (MRT), consistent with its roles in cell-adhesion and migration programs that are dysregulated following SMARCB1 loss.

Alterations observed in the corpus

  • Among the most over-expressed genes in mRNA sub-group 2 (cell adhesion/migration, WNT, differentiation) of extra-cranial MRT with SMARCB1 biallelic inactivation PMID:26977886
  • Mesenchymal-transition transcript up-regulated in pre-treatment non-responding melanoma (SKCM) tumors; co-enriched within the IPRES innate anti-PD-1 resistance transcriptional signature alongside AXL, ROR2, LOXL2, TWIST2 PMID:26997480.
  • Overexpressed in MAML3 fusion-positive PCC/PGL tumors as part of the Wnt/Hedgehog activation signature of the Wnt-altered molecular subtype; upregulation linked to promoter hypomethylation driven by aberrant MAML3 expression (p < 4e-10) PMID:28162975

Cancer types (linked)

  • Malignant rhabdoid tumor (MRT): WNT5A is highly over-expressed in mRNA sub-group 2, which parallels the RTK sub-type of AT/RT and is characterized by WNT pathway, cell-adhesion, and differentiation gene signatures PMID:26977886.
  • SKCM: WNT5A up-regulation characterizes innate anti-PD-1 resistant tumors; component of IPRES mesenchymal-transition program PMID:26997480.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No direct therapeutic relevance established; non-canonical WNT pathway activation via WNT5A in MRT is hypothesis-generating PMID:26977886

Open questions

  • Whether WNT5A over-expression is mechanistically linked to SMARCB1 loss or represents an independent transcriptional program is unresolved PMID:26977886

Sources

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