Language
English
Publication Date
10-1-2025
DOI
10.1038/s42255-025-01368-w
PMID
40973819
PMCID
PMC12552132
PubMedCentral® Posted Date
9-19-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The consumption of sugar-sweetened beverages (SSBs), which contain high levels of fructose and glucose, has been causally and mechanistically linked to an increased risk of colorectal cancer (CRC). However, the effects of SSB consumption on advanced stages of disease progression, including metastasis, remain poorly understood. Here we show that exposure of CRC cells to a glucose and fructose formulation-reflecting the composition of both high-fructose corn syrup and sucrose found in SSBs-enhances cellular motility and metastatic potential compared to glucose alone. Given that CRC cells grow poorly in fructose alone, and cells in vivo are not physiologically exposed to fructose without glucose, we excluded the fructose-only condition from our studies unless needed as a control. Mechanistically, the combination of glucose and fructose elevates the NAD⁺/NADH ratio by activation of the reverse reaction of sorbitol dehydrogenase in the polyol pathway. This redox shift relieves NAD⁺ limitations and accelerates glycolytic activity, which in turn fuels activation of the mevalonate pathway, ultimately promoting CRC cell motility and metastasis. Our findings highlight the detrimental impact of SSBs on CRC progression and suggest potential dietary and therapeutic strategies to mitigate metastasis in patients with CRC.
Keywords
Colorectal Neoplasms, Fructose, Glucose, Humans, Animals, Neoplasm Metastasis, Cell Movement, Sugar-Sweetened Beverages, Mice, Cell Line, Tumor, Glycolysis, NAD, Cancer metabolism, Colorectal cancer, Metabolism, Metabolomics
Published Open-Access
yes
Recommended Citation
Feng, Tianshi; Luo, Qin; Liu, Yanlin; et al., "Fructose and Glucose From Sugary Drinks Enhance Colorectal Cancer Metastasis via SORD" (2025). Faculty and Staff Publications. 5592.
https://digitalcommons.library.tmc.edu/baylor_docs/5592
Included in
Allergy and Immunology Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Oncology Commons, Pathology Commons