Wnt Signaling Pathway in Colorectal and Oral Cancers

The Wnt signalling pathway is a pivotal regulator of cell fate, proliferation and differentiation across diverse tissues. In colorectal carcinogenesis, aberrations in the canonical Wnt cascade, most commonly via inactivating mutations in the tumour suppressor gene APC, lead to stabilisation of cytoplasmic β-catenin and its translocation to the nucleus. There it drives transcription of oncogenic target genes such as MYC and CCND1, promoting unchecked epithelial proliferation, loss of cell adhesion, epithelial–mesenchymal transition (EMT) and eventual invasion. Such dysregulation occurs at the earliest stages of adenoma formation and persists through metastatic progression, rendering components of the pathway attractive biomarkers and therapeutic targets. In the oral cavity, progressive activation of Wnt/β-catenin signalling is observed during the transition from normal mucosa to dysplasia and carcinoma. Nuclear accumulation of β-catenin correlates with grades of oral epithelial dysplasia and signals a shift towards malignancy. Cross-talk with endocytic trafficking, epigenetic modulation and other pathways further refines Wnt-driven tumour behaviour, and underlies the quest for pathway inhibitors or agents that restore regulatory feedback. The global significance of Wnt signalling in colorectal and oral cancers is underlined by its recurrent involvement in tumour initiation, progression and resistance to conventional therapies, spurring efforts to translate mechanistic understanding into clinical advances.

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Wnt Signaling Pathway in Colorectal and Oral Cancers publication trend

The graph below shows the total number of articles in wnt signaling pathway in colorectal and oral cancers across all publications each year (not limited to Nature Index journals).

Technical terms

Canonical Wnt signalling: A pathway in which Wnt ligands bind receptors to prevent β-catenin degradation, allowing it to enter the nucleus and regulate gene expression.

β-catenin: A dual-function protein that mediates cell–cell adhesion at the membrane and acts as a transcriptional co-activator in the nucleus upon pathway activation.

Adenomatous polyposis coli (APC): A tumour suppressor that targets β-catenin for degradation; loss-of-function mutations lead to aberrant pathway activation.

Epithelial–mesenchymal transition (EMT): A phenotypic switch in which epithelial cells acquire mesenchymal traits, enhancing migratory and invasive capabilities.

Dysplasia: A premalignant alteration in epithelial cells characterised by abnormal morphology and increased proliferative activity.

References

1. Recurrent UBE3C-LRP5 translocations in head and neck cancer with therapeutic implications. npj Precision Oncology (2024).
2. Wnt/β-Catenin Signaling in Oral Carcinogenesis. International Journal of Molecular Sciences (2020).
3. Prognostic Significance of β-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series. Frontiers in Oncology (2014).