{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWNT6 acts as a potent signaling molecule in cancer by activating the canonical Wnt/β‐catenin pathway and other oncogenic cascades. In gastric cancer, for example, WNT6 over‐expression—enhanced by caveolin‑1—confers resistance to chemotherapeutic‐induced apoptosis, while in colorectal cancer, its transcription is upregulated by PLAGL2 to drive tumor proliferation. In glioblastoma, WNT6 increases cell viability, invasion, migration, stem cell characteristics, and chemoresistance; similarly, its aberrant expression in esophageal squamous cell carcinoma, osteosarcoma, ovarian cancer, and even breast cancer correlates with poor clinical outcomes. Genetic variability in WNT6 (including SNPs) further associates with predisposition to colorectal adenoma development. In glioma, deregulated DNA methylation and HOXA9‐mediated transcription lead to increased WNT6 levels and aggressive tumor behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic roles, WNT6 is critical in developmental and tissue homeostatic processes, particularly within the craniofacial and dental domains. It contributes to tooth morphogenesis and dental tissue mineralization, as evident from its involvement in dental papilla cell differentiation and dental pulp repair—processes that engage both canonical and non‐canonical signals (e.g., via JNK activation). Moreover, alterations in WNT6 (or its genetic variants) have been associated with congenital conditions such as isolated oral clefts and dental pulp calcification, while its preferential expression in the limbal stem cell niche suggests a role in corneal epithelium maintenance and regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn additional contexts, WNT6 is implicated in metabolic and reproductive processes. Pathophysiological factors of type 2 diabetes—including high glucose, insulin, palmitic acid, and advanced glycation end products—induce WNT6 secretion that, in turn, activates β‐catenin signaling and promotes centrosome amplification. Furthermore, preliminary evidence has raised the possibility that mutations or polymorphisms in WNT6 may influence reproductive outcomes such as unexplained recurrent miscarriage, and alterations in its expression are being examined in the setting of early pregnancy loss."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rachel L Galbraith, Elizabeth M Poole, David Duggan, et al. 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