NKD1
Overview
NKD1 (Naked Cuticle Homolog 1) encodes a WNT signaling antagonist that inhibits the pathway by interacting with Dishevelled proteins. It functions as a negative regulator of canonical WNT/β-catenin signaling. In prostate cancer, NKD1 has been identified as a WNT-pathway gene silenced by EZH2-mediated epigenetic repression in neuroendocrine prostate cancer (CRPC-NE).
Alterations observed in the corpus
- WNT-pathway EZH2 target significantly down-regulated in CRPC-NE (P = 0.0046) PMID:26855148
- NKD1 identified as part of the Wnt/Hedgehog signaling network activated by MAML3 fusion genes in the Wnt-altered pheochromocytoma/paraganglioma subtype PMID:28162975
Cancer types (linked)
- CRPC-NE (castration-resistant prostate cancer — neuroendocrine): NKD1 significantly down-regulated vs. CRPC-Adeno (P = 0.0046); repression mediated by EZH2 PMID:26855148
Co-occurrence and mutual exclusivity
- NKD1 down-regulation co-occurs with EZH2 overexpression and RB1/TP53 loss in CRPC-NE PMID:26855148
Therapeutic relevance
- NKD1 expression restored by EZH2 inhibitor GSK343 in NCI-H660 neuroendocrine prostate cancer cells PMID:26855148
Open questions
- Whether NKD1 loss functionally contributes to WNT pathway activation in CRPC-NE, or is purely a bystander effect of global EZH2 silencing, is not established.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:28162975
This page was processed by entity-page-writer on 2026-05-15.