Work

Dietary targeting of CNBP to rein in the EREG-EGFR cascade and restore homeostasis in colitis-associated colorectal cancer

Year: 2026

Type: article

Abstract: Emerging evidence has linked high dietary fructose intake with adverse health outcomes, yet its role in colitis-associated colorectal cancer (CAC) remains underexplored.Here, we demonstrate that high fructose consumption aggravates intestinal inflammation and significantly promotes tumorigenesis in an AOM/DSS-induced CAC model via activation of the EREG-EGFR signaling axis.We first developed the Food∩TCM database, which encompasses 112 medicine and food homologous TCM, along with their chemical compositions.Using the network-based pharmacological intelligence platform, we identified Laminaria japonica (kelp) and its bioactive components-fucoidan and dieckol-as promising dietary interventions.Dieckol was found to target the RNA/DNA-binding protein CNBP, which has traditionally been regarded as a positive regulator of pro-inflammatory gene expression, but here was shown to enhance its nuclear localization under inflammatory conditions and thereby repress Ereg transcription.Notably, fructose promoted O-GlcNAcylation-mediated stabilization and secretion of EREG in inflammatory fibroblasts, contributing to tumor progression.Together, these findings reveal the tumor-promoting effects of dietary fructose in CAC and highlight CNBP as a key regulator restraining Ereg expression.Our findings underscore the significance of integrating food-based strategies into chronic disease prevention, and support the development of Laminaria japonica-derived compounds as safe, long-term dietary agents for managing colitis-associated colorectal cancer.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.128354