Drink Responsibly: Cancer Cells Also Like Sugary Drinks.

Abstract

Sugar-sweetened beverages (SSB), which contain both glucose and fructose, have been linked to an increased incidence of colorectal cancer. Their effects on colorectal cancer progression, however, are unclear. In their recent work, Feng and colleagues investigated how exposure to SSBs affects colorectal cancer metastasis. They discovered that several colorectal cancer cell lines showed enhanced migration when exposed to glucose and fructose together, compared with cells exposed to glucose or fructose alone. Similarly, in mouse models of colorectal cancer liver metastasis, mice fed both glucose and fructose developed more liver metastases, suggesting that SSBs promote colorectal cancer spread. Leveraging metabolomic analyses, they discovered that in the presence of both glucose and fructose, the enzyme sorbitol dehydrogenase (SORD) converts fructose to sorbitol, regenerating NAD+ from NADH. Deleting SORD reduced the NAD+/NADH ratio and colorectal cancer cell migration and metastasis. Restoring the NAD+/NADH ratio rescued migration, suggesting that SORD-driven NAD+ regeneration promotes metastatic behavior. Furthermore, they demonstrated that increased NAD+/NADH levels have a profound effect on cell metabolism, supporting glycolysis, the TCA cycle, and the mevalonate pathway. Interestingly, pharmacologic inhibition of the mevalonate pathway with statins reduced cell migration and liver metastasis in mice consuming SSBs. Together, these findings demonstrate that SSBs enhance colorectal cancer metastasis through SORD-dependent metabolic reprogramming. By regenerating NAD+ and glycolysis and supporting the mevalonate pathway, SORD links SSB consumption to increased tumor cell migration and metastatic potential.