Protein naked cuticle homolog 1 (NKD1) (NKD1)

Protein naked cuticle homolog 1 (NKD1) is a crucial negative feedback regulator of the Wnt signaling pathway, which plays a fundamental role in embryonic development and tissue regeneration [1, 2, 8]. NKD1 acts by binding to Dishevelled (Dvl) and beta-catenin, thereby preventing the nuclear translocation of beta-catenin and inhibiting the transcription of Wnt-responsive genes [5, 12, 17]. Although it typically functions as a tumor suppressor, its role in oncology is complex and tissue-specific [9, 11]. In glioblastoma and hepatocellular carcinoma, reduced NKD1 levels are linked to poor clinical outcomes, whereas in colorectal cancer, high NKD1 expression may actually promote tumor growth by stabilizing the MYC protein [6, 9, 11]. As a result, NKD1 is an emerging target for therapeutic intervention and a potential biomarker for patient stratification in Wnt-driven diseases [13, 15].

Other names

Naked-1Naked1Dvl-binding proteinNKD inhibitor of Wnt signaling pathway 1hNkd1

Antagonism of the Wnt signaling pathway by binding to Dishevelled (Dvl) and beta-catenin, thereby preventing the nuclear translocation of beta-catenin and inhibiting Wnt-mediated gene transcription [1, 5, 12].